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  • 1.
    Ahl, David
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Eriksson, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Sedin, John
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Seignez, Cedric
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Schwan, Emil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Kreuger, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Christoffersson, Gustaf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Phillipson, Mia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Turning Up the Heat: Local Temperature Control During in vivo Imaging of Immune Cells2019Ingår i: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 10, artikel-id 2036Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Intravital imaging is an invaluable tool for studying the expanding range of immune cell functions. Only in vivo can the complex and dynamic behavior of leukocytes and their interactions with their natural microenvironment be observed and quantified. While the capabilities of high-speed, high-resolution confocal and multiphoton microscopes are well-documented and steadily improving, other crucial hardware required for intravital imaging is often developed in-house and less commonly published in detail. In this report, we describe a low-cost, multipurpose, and tissue-stabilizing in vivo imaging platform that enables sensing and regulation of local tissue temperature. The effect of tissue temperature on local blood flow and leukocyte migration is demonstrated in muscle and skin. Two different models of vacuum windows are described in this report, however, the design of the vacuum window can easily be adapted to fit different organs and tissues.

  • 2.
    Ahlgren, Kerstin. M
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Fall, Tove
    Landegren, Nils
    von Euler, Henrik
    Sundberg, Katarina
    Lindblad-Toh, Kerstin
    Lobell, Anna
    Hedhammar, Åke
    Andersson, Göran
    Hansson-Hamlin, Helene
    Lernmark, Åke
    Kämpe, Olle
    Diabetes mellitus in dog -: No evidence for a type-1-like phenotypeManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Aims/hypothesis

    Diabetes mellitus (DM) is one of the most common endocrine disorders in dogs, and is commonly proposed to be of autoimmune origin. Although the clinical symptoms of human type 1 diabetes (T1D) and canine DM are similar, the aetiologies may differ. The aim of this study was to investigate if autoimmune aetiology resembling human T1D is as prevalent in dogs as previously reported.

    Methods

     Sera from 121 diabetic dogs representing 38 different breeds were tested for islet cell antibodies (ICA) and GAD65 autoantibodies (GADA) and compared with sera from 133 healthy dogs from 40 breeds. ICA was detected by indirect immunofluorescence using both canine and human frozen sections. GADA was detected by in vitro transcription and translation (ITT) of human and canine GAD65, followed by immunoprecipitation.

    Results

    None of the canine sera analyzed tested positive for ICA on sections of frozen canine or human ICA pancreas. However, serum from one diabetic dog was weakly positive in the canine GADA assay and serum from one healthy dog was weakly positive in the human GADA assay.

    Conclusions/interpretations

    Based on sera from 121 diabetic dogs from 38 different breeds were tested for humoral autoreactivity using four different assays, contrary to previous observations, we find no support for an autoimmune aetiology  in canine diabetes.

  • 3.
    Ahlström, Anna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för biologisk grundutbildning.
    Testing the specificity of the pBAD arabinose reporter2017Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
    Abstract [en]

    The project highlights Salmonella enterica subspecies enterica serovar Typhimurium (S. Tm)'s ability to metabolize simple sugars released from dead commensal bacteria, by using the pBAD (araBAD promoter) system as a reporter of L-arabinose availability. Using bioinformatics and homology of conserved L-arabinose transporter genes shared in Escherichia coli K12 (E. coli) and S. Tm, we aimed to create a S. Tm mutant strain unable to obtain L-arabinose from it environment. During the projects course of time it was discovered that L-arabinose transporters are not a shared gene trait between E. coli and S. Tm, and that putative L-arabinose transporter orthologues may exists in the S. Tm genome.

  • 4.
    Akula, Srinivas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för biologisk grundutbildning.
    Analysis of the isotype specificity of three platypus immunoglobulin Fc receptors2012Självständigt arbete på avancerad nivå (masterexamen), 30 poäng / 45 hpStudentuppsats (Examensarbete)
    Abstract [en]

    The host’s defense against diseases called immunity acts either via innate or adaptive defense mechanisms. Immunoglobulins (Ig’s) are important players in adaptive immunity. They have evolved both structurally and functionally during vertebrate evolution. The Fc region of Igs can interact with specific receptors on the surface of various immune cells; crosslinking of these Fc receptors can trigger a wide array of immune reactions. To trigger such reactions, higher mammals have five different classes of Igs (IgM, IgG, IgA, IgE and IgD) while amphibians, reptiles and birds have four (IgM, IgD, IgA and IgY).  Our recent studies have revealed that the early mammals (Platypus) have eight Ig isotypes (IgM, IgD IgO, IgG1, IgG2, IgA1, IgA2 and IgE) and at least four Fc receptors: FcRA, FcRB, FcRC and FcRD. In this study we investigated the specificity of three of these platypus Fc receptors to get a better picture of their isotype specificity.   

  • 5.
    Akula, Srinivas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi. Uppsala University.
    The mast cell transcriptome and the evolution of granule proteins and Fc receptors2019Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Protection against disease-causing pathogens, known as immunity, involves numerous cells organs, tissues and their products. To able to understand the biology of immune cells (hematopoietic cells) and their role in an immune system, we have used several different methods, including transcriptome analyses, bioinformatics, production of recombinant proteins and analyses of some of them, focusing on the granule proteases by substrate phage display.

    Hematopoietic cells express surface receptors interacting with the constant region of immunoglobulins (Igs) known as Fc receptors (FcRs). These receptors play major roles in the immune system, including enhancing phagocytosis, activating antibody dependent cellular cytotoxicity and cell activation. A detailed bioinformatics analysis of FcRs reveals that the poly-Ig receptors (PIGR), FcR-like molecules and common signalling γ chain all appeared very early with the appearance of the bony fishes, and thereby represent the first major evolutionary step in FcR evolution. The FcμR, FcαμR, FcγR and FcεR receptors most likely appeared in reptiles or early mammals, representing the second major step in FcR evolution.

    Cells of several of the hematopoietic cell lineages contain large numbers of cytoplasmic granules, and serine proteases constitute the major protein content of these granules. In mammals, these proteases are encoded from four different loci: the chymase, the met-ase, the granzyme (A/K) and the mast cell tryptase loci. The granzyme (A/K) locus was the first to appear and came with the cartilaginous fishes. This locus is also the most conserved of the three. The second most conserved locus is the met-ase locus, which is found in bony fishes. The chymase locus appeared relatively late, and we find the first traces in frogs, indicating it appeared in early tetrapods.

    To study the early events in the diversification of these hematopoietic serine proteases we have analyzed key characteristics of a protease expressed by an NK-like cell in the channel catfish, catfish granzyme–like I. We have used phage display and further validated the results using a panel of recombinant substrates. This protease showed a strict preference for Met at the P1 (cleavage) position, which indicates met-ase specificity. From the screening of potential in vivo substrates, we found an interesting potential target caspase 6, which indicates that caspase-dependent apoptosis mechanisms have been conserved from fishes to mammals.

    A larger quantitative transcriptome analysis of purified mouse peritoneal mast cells, cultured mast cells (BMMCs), and mast cells isolated from mouse ear and lung tissue identified the major tissue specific transcripts in these mast cells as the granule proteases. Mast cell specific receptors and processing enzymes were expressed at approximately 2 orders of magnitude lower levels. The levels of a few proteases were quite different at various anatomical sites between in vivo and cultured BMMCs. These studies have given us a new insights into mast cells in different tissues, as well as key evolutionary aspects concerning the origins of a number of granule proteases and FcRs.

    Delarbeten
    1. Fc Receptors for Immunoglobulins and Their Appearance during Vertebrate Evolution
    Öppna denna publikation i ny flik eller fönster >>Fc Receptors for Immunoglobulins and Their Appearance during Vertebrate Evolution
    2014 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 5, s. e96903-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Receptors interacting with the constant domain of immunoglobulins (Igs) have a number of important functions in vertebrates. They facilitate phagocytosis by opsonization, are key components in antibody-dependent cellular cytotoxicity as well as activating cells to release granules. In mammals, four major types of classical Fc receptors (FcRs) for IgG have been identified, one high-affinity receptor for IgE, one for both IgM and IgA, one for IgM and one for IgA. All of these receptors are related in structure and all of them, except the IgA receptor, are found in primates on chromosome 1, indicating that they originate from a common ancestor by successive gene duplications. The number of Ig isotypes has increased gradually during vertebrate evolution and this increase has likely been accompanied by a similar increase in isotype-specific receptors. To test this hypothesis we have performed a detailed bioinformatics analysis of a panel of vertebrate genomes. The first components to appear are the poly-Ig receptors (PIGRs), receptors similar to the classic FcRs in mammals, so called FcRL receptors, and the FcR gamma chain. These molecules are not found in cartilagous fish and may first appear within bony fishes, indicating a major step in Fc receptor evolution at the appearance of bony fish. In contrast, the receptor for IgA is only found in placental mammals, indicating a relatively late appearance. The IgM and IgA/M receptors are first observed in the monotremes, exemplified by the platypus, indicating an appearance during early mammalian evolution. Clearly identifiable classical receptors for IgG and IgE are found only in marsupials and placental mammals, but closely related receptors are found in the platypus, indicating a second major step in Fc receptor evolution during early mammalian evolution, involving the appearance of classical IgG and IgE receptors from FcRL molecules and IgM and IgA/M receptors from PIGR.

    Nationell ämneskategori
    Biomedicinsk laboratorievetenskap/teknologi
    Identifikatorer
    urn:nbn:se:uu:diva-228481 (URN)10.1371/journal.pone.0096903 (DOI)000336838000078 ()
    Tillgänglig från: 2014-07-15 Skapad: 2014-07-15 Senast uppdaterad: 2019-04-12Bibliografiskt granskad
    2. Granule Associated Serine Proteases of Hematopoietic Cells - An Analysis of Their Appearance and Diversification during Vertebrate Evolution
    Öppna denna publikation i ny flik eller fönster >>Granule Associated Serine Proteases of Hematopoietic Cells - An Analysis of Their Appearance and Diversification during Vertebrate Evolution
    2015 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 11, artikel-id e0143091Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Serine proteases are among the most abundant granule constituents of several hematopoietic cell lineages including mast cells, neutrophils, cytotoxic T cells and NK cells. These proteases are stored in their active form in the cytoplasmic granules and in mammals are encoded from four different chromosomal loci: the chymase locus, the met-ase locus, the T cell tryptase and the mast cell tryptase locus. In order to study their appearance during vertebrate evolution we have performed a bioinformatic analysis of related genes and gene loci from a large panel of metazoan animals from sea urchins to placental mammals for three of these loci: the chymase, met-ase and granzyme A/K loci. Genes related to mammalian granzymes A and K were the most well conserved and could be traced as far back to cartilaginous fish. Here, the granzyme A and K genes were found in essentially the same chromosomal location from sharks to humans. However in sharks, no genes clearly identifiable as members of the chymase or met-ase loci were found. A selection of these genes seemed to appear with bony fish, but sometimes in other loci. Genes related to mammalian met-ase locus genes were found in bony fish. Here, the most well conserved member was complement factor D. However, genes distantly related to the neutrophil proteases were also identified in this locus in several bony fish species, indicating that this locus is also old and appeared at the base of bony fish. In fish, a few of the chymase locus-related genes were found in a locus with bordering genes other than the mammalian chymase locus and some were found in the fish met-ase locus. This indicates that a convergent evolution rather than divergent evolution has resulted in chymase locus-related genes in bony fish.

    Nationell ämneskategori
    Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
    Identifikatorer
    urn:nbn:se:uu:diva-271027 (URN)10.1371/journal.pone.0143091 (DOI)000365070700134 ()26569620 (PubMedID)
    Forskningsfinansiär
    Vetenskapsrådet, 621-2011-5007
    Tillgänglig från: 2016-01-05 Skapad: 2016-01-05 Senast uppdaterad: 2019-04-12Bibliografiskt granskad
    3. Channel catfish granzyme-like I is a highly specific serine protease with metase activity that is expressed by fish NK-like cells
    Öppna denna publikation i ny flik eller fönster >>Channel catfish granzyme-like I is a highly specific serine protease with metase activity that is expressed by fish NK-like cells
    2016 (Engelska)Ingår i: Developmental And Comparative Immunology, ISSN 0145-305X, Vol. 63, s. 84-95Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Here we present the extended cleavage specificity of catfish granzyme-like I, previously identified in fish NK-like cells. This protease has been characterised using substrate phage display and further validated by using a panel of recombinant substrates. A strict preference for Met in the P1 (cleavage) position, indicating metase specificity was observed. A screening of potential in vivo substrates was performed based on the derived P5-P3' consensus: Arg-Val-Thr-Gly-Met(down arrow)Ser-Leu-Val. Channel catfish caspase 6 was one very interesting potential target identified. This site was present in an adjacent position to the classic caspase activation site (Asp179 in human caspase 6). Cleavage of this site (hence potential activation) by the catfish granzyme-like I could reveal a novel mechanism of caspase 6 activation. This poses an interesting idea that the role of granzyme-like proteases in the activation of caspase dependent apoptosis mechanisms has been conserved for over 400 million years.

    Nyckelord
    Fish; Serine protease; Cleavage specificity; Metase; NK cell; Caspase; Evolution
    Nationell ämneskategori
    Immunologi
    Identifikatorer
    urn:nbn:se:uu:diva-221554 (URN)10.1016/j.dci.2016.05.013 (DOI)000380623300010 ()27216028 (PubMedID)
    Forskningsfinansiär
    Vetenskapsrådet, 621-2011-5007
    Tillgänglig från: 2014-04-09 Skapad: 2014-04-01 Senast uppdaterad: 2019-04-12Bibliografiskt granskad
    4. The mouse mast cell transcriptome
    Öppna denna publikation i ny flik eller fönster >>The mouse mast cell transcriptome
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Mast cells (MCs) are highly specialized tissue resident cells that are often found at the interphase between body and environment such as the skin, lung and intestinal mucosa. To obtain a more detailed picture of the biology of MCs we have analyzed the transcriptome of MCs from different mouse organs by RNA-seq and PCR based transcriptomics.  The results show that MCs at different tissue locations can differ quite substantially in transcript levels of several of the most abundant granule proteins even if they belong to the same basic MC type, i.e connective tissue or mucosal MCs. We can also see that transcript levels for the major granule proteins, like the various proteases and the heparin core protein can be several orders of magnitude higher than the surface receptors.  This also applies for the processing enzymes involved in activation of the proteases and in the synthesis of heparin and histamine. Interestingly also is the almost complete absence of transcripts for cytokines in the MC populations of the various organs, indicating that cytokines only are produced by activated MCs. Bone marrow derived MCs are often used as equivalents of tissue MCs.  We here show that these cells differ substantially in their transcriptome from tissue MCs. They show a transcriptome of relatively immature cells both with respect to the granule components and to the processing enzymes indicating that care should be taken when transferring findings from these cells to the in vivo function of tissue resident MCs.  This latter finding also give clear indication for that additional cytokines are needed, in addition to the stem cell factor (SCF), for the development into fully mature tissue MCs.

    Nationell ämneskategori
    Cell- och molekylärbiologi
    Forskningsämne
    Immunologi
    Identifikatorer
    urn:nbn:se:uu:diva-381501 (URN)
    Tillgänglig från: 2019-04-11 Skapad: 2019-04-11 Senast uppdaterad: 2019-04-15Bibliografiskt granskad
  • 6.
    Allkja, Jontana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    The influence of copper on mast cell during bacterial infections2017Självständigt arbete på avancerad nivå (masterexamen), 30 poäng / 45 hpStudentuppsats (Examensarbete)
    Abstract [en]

    Mast cells are innate immune cells generally known for their harmful effects, particularly their role in asthma and autoimmune diseases. However, they can also recognize pathogens and mount a response to them. Copper is essential for proper cell function and homeostasis. Research has shown that changes in copper levels can affect mast cell morphology and gene expression of many of its immune mediators. It has also been shown that the copper transporter Ctr2 plays an important role in mast cell physiology. In this project, we investigated whether the same effects can be seen when mast cells are stimulated with bacteria, namely Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). For this purpose, wild type and Ctr2 knockout mast cells were treated with different concentrations of copper for 72 hours and later co-cultured with either S. aureus or E. coli. Wild type cells were also treated with a copper chelator to investigate the effect of copper starvation. Release of IL-6 and CCL2, two common mediators released in response to bacteria, were measured by ELISA, while their gene expression was measured by qPCR. Results showed that either copper starvation or, 10 μM copper cause an increase in IL-6 and CCL2 protein levels, but have no effect on gene expression. The 10 μM copper effect was not observed in the Ctr2 knockout cells. In conclusion, not much is known about the mechanisms involved in the mast cell response to bacteria. However, it appears that copper can affect either different stages of the same pathway, or different pathways in a similar manner.

  • 7.
    Almgren, Johanna
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Characterization of antibodies against mustard and development of immunological methods for the detection and quantification of mustard in foods2007Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats
    Abstract [en]

    ABSTRACT

    Allergy to mustard has been reported for many years, in some cases as severe anaphylactic reactions. Recent studies imply that this allergy is increasing. Three major allergens have been isolated and characterised; Sin a 1 and Sin a 2 in yellow mustard (Sinapis alba), and Bra j 1 in oriental mustard (Brassica juncea). Yellow mustard and black mustard (Brassica nigra) are the most common species in Europe, whereas oriental mustard is more frequent outside Europe. Mustard plants belong to the Brassicaceae/Cruciferae family. Mustard is present as an ingredient in different foods, sauces and spices, often in small amounts. According to the European labelling directives, mustard and products thereof must always be declared. To monitor this regulation, methods need to be developed to detect mustard. Polyclonal antibodies, produced in rabbits, against yellow and black mustard were characterised with immunodiffusion, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions, and immunoblotting. Rocket-immunoelectrophoresis and enzyme-linked immunosorbent assay (ELISA) were developed for the detection and quantification of mustard protein. With indirect competitive ELISA a concentration of 156ng mustard protein per ml food extract was detected, which is more than enough to cover the lowest reported reactive doses.

  • 8.
    Alvarado-Vazquez, Perla Abigail
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Grosick, Rachel L.
    Presbyterian Coll, Sch Pharm, Dept Pharm Practice, Clinton, SC USA.
    Moracho-Vilrriales, Carolina
    Presbyterian Coll, Sch Pharm, Dept Pharm Practice, Clinton, SC USA.
    Ward, Eileen
    Presbyterian Coll, Sch Pharm, Dept Pharm Practice, Clinton, SC USA.
    Threatt, Tiffaney
    Presbyterian Coll, Sch Pharm, Dept Pharm Practice, Clinton, SC USA.
    Romero-Sandoval, Edgar Alfonso
    Wake Forest Univ, Sch Med, Pain Mech Lab, Dept Anesthesiol, 1 Med Ctr Blvd, Winston Salem, NC 27157 USA.
    Cytokine production capabilities of human primary monocyte-derived macrophages from patients with diabetes mellitus type 2 with and without diabetic peripheral neuropathy2019Ingår i: Journal of Pain Research, ISSN 1178-7090, E-ISSN 1178-7090, Vol. 12, s. 69-81Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Monocytes from patients with diabetes mellitus type 2 (DM2) are dysfunctional, persistently primed, and prone to a proinflammatory phenotype. This may alter the phenotype of their differentiation to macrophages and result in diabetic peripheral neuropathy (DPN), nerve damage, nerve sensitization, and chronic pain. We have previously demonstrated that CD163 is a molecule that promotes an anti-inflammatory cellular phenotype in human primary macrophages, but this has not been proven in macrophages from patients with DM2 or DPN. Thus, we hypothesize that macrophages from patients with DM2 or DPN display an altered proinflammatory functional phenotype related to cytokine production and that the induction of CD163 expression will promote a more homeostatic phenotype by reducing their proinflammatory responsiveness.

    Patients and methods: We tested these hypotheses in vitro using blood monocyte-derived macrophages from healthy subjects and patients with DM2 with and without DPN. Cells were incubated in the presence or the absence of 5 mu g/mL of lipopolysaccharide (LPS). The concentrations of interleuldn-10, interleukin-6, tumor necrosis factor-alpha (TNF-alpha), TGF-beta, and monocyte chemoattractant protein-1 (MCP-1) were measured using ELISA assays. Macrophages were transfected with an empty vector plasmid or a plasmid containing the CD163 gene using mannosylated polyethylenimine nanoparticles.

    Results: Our results show that nonstimulated DM2 or DPN macrophages have a constitutive primed proinflammatory state and display a deficient production of proinflammatory cytokines upon a proinflammatory challenge when compared to healthy macrophages. CD163 induction produced an anti-inflammatory phenotype in the healthy control group, and this effect was partial in DM2 or DPN macrophages.

    Conclusion: Our results suggest that diabetic macrophages adopt a complex phenotype that is only partially reversed by CD163 induction. Future experiments are focused on elucidating this differential responsiveness between healthy and diabetic macrophages.

  • 9.
    Andersson, Måns Sverker
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för ekologi och evolution. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för ekologi och evolution, Zooekologi. zooekologi.
    Gustafsson, Lars
    Glycosylated haemoglobin: a new measure of condition in birds1995Ingår i: Proceedings of the Royal Society of London, nr 260, s. 299-303Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Abstract: The influence of condition on time of breeding and reproductive success has been discussed since Darwin first suggested a relation in 1871. We used a novel method to investigate the influence of condition on the timing of breeding and reproductive success by measuring a relatively inert physiological parameter - the amount of glycosylated haemoglobin - in blood samples taken from the collared flycatcher Ficedula albicollis. The percentage of glycosylated haemoglobin (%HbG) was assumed to be proportional to the average blood glucose level, during the 3-5 weeks before the blood sampling. The %HbG was influenced neither by sex nor age. Date of arrival at the breeding ground was negatively correlated with %HbG so that early-arriving birds had significantly higher %HbG than those arriving later. Clutch size, corrected for the effect of laying date, correlated positively with %HbG in females, as did the number of fledged young, corrected for the effect of laying date, for both sexes. We found no correlation between body mass and the %HbG. We suggest that prebreeding condition influences the timing of breeding and subsequent reproductive performance and that %HbG can be used as an indicator of prebreeding-condition in migrating birds.

  • 10.
    Angthong, Pacharaporn
    et al.
    Chulalongkorn Univ, Program Biotechnol, Fac Sci..
    Roytrakul, Sittiruk
    Natl Sci & Technol Dev Agcy, Natl Ctr Genet Engn & Biotechnol BIOTEC..
    Jarayabhand, Padermsak
    Chulalongkorn Univ, Grad Sch, Interdisciplinary Grad Program Maritime Adm..
    Jiravanichpaisal, Pikul
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Jämförande fysiologi.
    Characterization and function of a tachylectin 5-like immune molecule in Penaeus monodon2017Ingår i: Developmental and Comparative Immunology, ISSN 0145-305X, E-ISSN 1879-0089, Vol. 76, s. 120-131Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Tachylectin5A and its homolog, tachylectin5B both contain a fibrinogen-related domain (FReD) and have been studied in horseshoe crabs, Tachypleus tridentatus and Carcinoscorpius rotundicauda and shown to be involved in host defense. Here, we demonstrate the presence of tachylectin5-like genes in shrimp, Penaeus monodon, designated as Penlectin5-1 (PL5-1) and Penlectin5-2 (PL5-2), which both contain a signal peptide and a single FReD with an acetyl group and a calcium binding sites and they are both structurally similar to horseshoe crab tachylectin/carcinolectin5. The PL5-land PL5-2 transcript were expressed in various shrimp tissues in normal shrimp, and their expression was upregulated in tissues such as hemocytes and hindgut following challenge with pathogenic Vibrio harveyi. The PL5-2 protein was detected in various tissues as well as in cell-free hemolymph. The biological function of the PL5-2 protein is to recognize some Gram-positive and Gram-negative bacteria regardless whether they are non-pathogenic or pathogenic. They have hemagglutination activity on human erythrocyte and bacterial agglutination activity to both Gram negative and Gram positive bacteria. Possible binding sites of PL5-2 to bacteria could be at the N-acetyl moiety of the G1cNAc-MurNAc cell wall of the peptidoglycan since the binding could be inhibited by G1cNAc or GaINAC. The presence of PL5-2 protein in both circulating hemolymph and intestine, where host and microbes are usually interacting, may suggest that the physiological function of shrimp tachylectin-like proteins is to recognize and bind to invading bacteria to immobilize and entrap these microbes and subsequently clear them from circulation and the host body, and probably to control and maintain the normal flora in the intestine.

  • 11.
    Angthong, Pacharaporn
    et al.
    Program in Biotechnology, Faculty of Science, Chulalongkorn University..
    Roytrakul, Sittiruk
    National Center for Genetic Engineering and Biotechnology (BIOTEC); National Science and Technology Development Agency (NSTDA)..
    Jarayabhand, Padermsak
    Interdisciplinary Graduate Program on Maritime Administration, Graduate School, Chulalongkorn University..
    Jiravanichpaisal, Pikul
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Jämförande fysiologi.
    Involvement of a tachylectin-like gene and its protein in pathogenesis of acute hepatopancreatic necrosis disease (AHPND) in the shrimp, Penaeus monodon2017Ingår i: Developmental and Comparative Immunology, ISSN 0145-305X, E-ISSN 1879-0089, Vol. 76, s. 229-237Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A shrimp disease, the so-called acute hepatopancreatic necrosis disease (AHPND) is caused by a specific strain of Vibrio parahaemolyticus (VP) and it has resulted in significant losses to the global shrimp farming industry. In our previous study, three of tachylectin-like genes were cloned and characterized from the intestine of Penaeus monodon, designated as Penlectin5-1 (PL5-1), Penlectin5-2 (PL5-2) and Penlectin5-3 (PL5-3). These three genes all contain fibrinogen-related domain (FReD). The expression level of PL5-1, PL5-2 and PL5-3 was elevated in the stomach after oral administration with AHPND-causing V. parahaemolyticus 3HP (VP3HP). A polyclonal antibody to PL5-2 was successfully produced in a rabbit using the purified recombinant P15-2 as an immunogen, and this because only the predominant protein PL5-2 could be successfully purified from shrimp plasma by affinity chromatography using a N-Acetyl-oglucosamine column allowed us to perform functional studies of this lectin. The native purified PL5-2 protein had binding and agglutination activities towards VP3HR To further understand the functions and the involvements of this lectin in response to AHPND in shrimp, RNAi-mediated knockdown of PL5-1, PL5-2 or PL5-3 was performed prior to an oral administration of VP3HP. As a result, Penlectin5-silencing in shrimp challenged with VP3HP showed higher mortality and resulted in more severe histopathological changes in the hepatopancreas with typical signs of AHPND. These results therefore suggest a role for crustacean fibrinogen-related proteins (FRePs) in innate immune response during the development of AHPND, and maybe also during other infections.

  • 12.
    Apitanyasai, Kantamas
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Jämförande fysiologi. Chulalongkorn Univ, Dept Biochem, Ctr Excellence Mol Biol & Genom Shrimp, Fac Sci, 254 Phayathai Rd, Bangkok 10330, Thailand..
    Noonin, Chadanat
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Jämförande fysiologi.
    Tassanakajon, Anchalee
    Chulalongkorn Univ, Dept Biochem, Ctr Excellence Mol Biol & Genom Shrimp, Fac Sci, 254 Phayathai Rd, Bangkok 10330, Thailand..
    Söderhäll, Irene
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Jämförande fysiologi.
    Söderhäll, Kenneth
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Jämförande fysiologi.
    Characterization of a hemocyte homeostasis-associated-like protein (HHAP) in the freshwater crayfish Pacifastacus leniusculus2016Ingår i: Fish and Shellfish Immunology, ISSN 1050-4648, E-ISSN 1095-9947, Vol. 58, s. 429-435Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Hemocyte homeostasis-associated-like protein (HHAP) in the freshwater crayfish Pacifastacus leniusculus has a distinct role from that of its homolog PmHHAP in the shrimp Penaeus monodon. Knockdown of PIHHAP in vitro using double-stranded RNA (dsRNA) had no effect on the cell morphology of hematopoietic tissue (HPT) cells. The total hemocyte number and caspase activity were unchanged after PIHHAP knockdown in vivo, in contrast to the results found in shrimp. Moreover, suppression of PIHHAP both in vitro and in vivo did not change the mRNA levels of some genes involved in hematopoiesis and hemocyte homeostasis. Interestingly, bacterial count and scanning electron microscope revealed that depletion of PIHHAP in intestine by RNAi resulted in higher number of bacteria in the crayfish intestine. Together, these results suggest that PIHHAP is not involved in hemocyte homeostasis in the crayfish P. leniusculus but appears to affect the bacterial number in the intestine through an unknown mechanism. Since PIHHAP has different functions from PmHHAP, we therefore named it HHAP-like protein.

  • 13. Bambou, Jean-Christophe
    et al.
    Giraud, Antoine
    Menard, Sandrine
    Begue, Bernadette
    Rakotobe, Sabine
    Heyman, Martine
    Taddei, François
    Cerf-Bensussan, Nadine
    Gaboriau-Routhiau, Valérie
    In vitro and ex vivo activation of the TLR5 signaling pathway in intestinal epithelial cells by a commensal Escherichia coli strain.2004Ingår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 279, nr 41, s. 42984-92Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The capacity of non-pathogenic enteric bacteria to induce a pro-inflammatory response is under debate in terms of its effect on the symbiosis between the mammalian host and its commensal gut microflora. Activation of NF-kappaB and induction of interleukin-8 (IL-8) and CCL-20 by the commensal Escherichia coli strain MG1655 were first studied in vitro in the human intestinal epithelial cell (IECs) lines HT29-19A and Caco-2, transfected or not with plasmids encoding dominant negative Toll-like receptor (TLR) 5 and myeloid differentiation factor-88 (MyD88) adaptor protein. The response of enterocytes in situ was then assessed using murine ileal biopsies mounted in Ussing chambers. Commensal E. coli induced NF-kappaB DNA binding, NF-kappaB transcriptional activity, CCL-20 expression, and IL-8 secretion in the human IEC lines. E. coli MG1655 flagellin was necessary and sufficient to trigger this pro-inflammatory pathway via its interaction with TLR5 and the subsequent recruitment of the adaptor protein MyD88. Following epithelial cell polarization, signaling could be induced by live E. coli and flagellin on the apical side of HT29-19A. The in vivo relevance of our findings was confirmed, because immunohistochemical staining of murine ileum demonstrated expression of TLR5 in the apical part of enterocytes in situ. Furthermore, flagellin added on the mucosal side of murine ileal biopsies mounted in Ussing chambers induced a basolateral production of KC, a functional murine homolog of human IL-8. These findings provide strong evidence that flagellin released by flagellated commensal bacteria in the intestinal lumen can induce a pro-inflammatory response in enterocytes in vivo.

  • 14.
    Barrenäs, Fredrik
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräknings- och systembiologi.
    Green, Richard R.
    Thomas, Matthew J.
    Law, G. Lynn
    Proll, Sean C.
    Engelmann, Flora
    Messaoudi, Ilhem
    Marzi, Andrea
    Feldmann, Heinz
    Katze, Michael G.
    Next-Generation Sequencing Reveals a Controlled Immune Response to Zaire Ebola Virus Challenge in Cynomolgus Macaques Immunized with Vesicular Stomatitis Virus Expressing Zaire Ebola Virus Glycoprotein (VSV Delta G/EBOVgp)2015Ingår i: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 22, nr 3, s. 354-356Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Vesicular stomatitis virus expressing Zaire Ebola virus (EBOV) glycoprotein (VSV Delta G/EBOVgp) could be used as a vaccine to meet the 2014 Ebola virus outbreak. To characterize the host response to this vaccine, we used mRNA sequencing to analyze peripheral blood mononuclear cells (PBMCs) from cynomolgus macaques after VSV Delta G/EBOVgp immunization and subsequent EBOV challenge. We found a controlled transcriptional response that transitioned to immune regulation as the EBOV was cleared. This observation supports the safety of the vaccine.

  • 15. Belov, Katherine
    et al.
    Hellman, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär immunologi. Molekylär immunologi.
    Immunoglobulin genetics of Ornithorhynchus anatinus (platypus) and Tachyglossus aculeatus (short-beaked echidna).2003Ingår i: Comp Biochem Physiol A Mol Integr Physiol, ISSN 1095-6433, Vol. 136, nr 4, s. 811-9Artikel i tidskrift (Refereegranskat)
  • 16.
    Belov, Katherine
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär immunologi. MOLECULAR IMMUNOLOGY, LARS HELLMAN.
    Hellman, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär immunologi.
    Platypus IgM and the divergence of the two extant monotreme lineages.2003Ingår i: Australian Mammology, Vol. 25, s. 87-94Artikel i tidskrift (Refereegranskat)
  • 17. Belov, Katherine
    et al.
    Hellman, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär immunologi. Molekylär immunologi.
    Cooper, D.W.
    Characterization of IgG from a monotreme, Tachyglossus aculeatus2002Ingår i: Immunogenetics, Vol. 53, s. 1065-1071Artikel i tidskrift (Refereegranskat)
  • 18. Belov, Katherine
    et al.
    Hellman, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär immunologi. Molekylär immunologi.
    Cooper, D.W.
    Characterization of of echidna IgM provides insight into the time of divergence of extant mammals.2002Ingår i: Developmental and Comparative Immunology, Vol. 26, s. 831-839Artikel i tidskrift (Refereegranskat)
  • 19. Belov, Katherine
    et al.
    Lam, Mary K P
    Hellman, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär immunologi. Molekylär immunologi.
    Colgan, Donald J
    Evolution of the major histocompatibility complex: Isolation of class II beta cDNAs from two monotremes, the platypus and the short-beaked echidna.2003Ingår i: Immunogenetics, ISSN 0093-7711, Vol. 55, nr 6, s. 402-11Artikel i tidskrift (Övrigt vetenskapligt)
  • 20. Belov, Katherine
    et al.
    Lam, MKP
    Hellman, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär immunologi. Molekylär Immunologi.
    Colgan, DJ.
    Evolution of the major histocompatibility complex: Isolation of class II _ cDNAs from two monotremes, the platypus and the short-beaked echidna.2003Ingår i: Immunogenetics, Vol. 55, s. 402-411Artikel i tidskrift (Refereegranskat)
  • 21. Belov, Katherine
    et al.
    Zenger, K.R.
    Hellman, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär immunologi. Molekylär immunologi.
    Cooper, D.W.
    Echidna IgA supports mammalian unity and traditional Therian relationship2002Ingår i: Mammalian Genome, Vol. 13, s. 656-663Artikel i tidskrift (Refereegranskat)
  • 22. Benton, Jeanne
    et al.
    Kery, Rachel
    Li, Jingjing
    Noonin, Chadanat
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Jämförande fysiologi.
    Söderhäll, Irene
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Jämförande fysiologi.
    Beltz, Barbara
    Cells from the Immune System Generate Adult-Born Neurons in Crayfish2014Ingår i: Developmental Cell, ISSN 1534-5807, E-ISSN 1878-1551, Vol. 30, nr 3, s. 322-333Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Neurogenesis is an ongoing process in the brains of adult decapod crustaceans. However, the first-generation precursors that produce adult-born neurons, which reside in a neurogenic niche, are not self-renewing in crayfish and must be replenished. The source of these neuronal precursors is unknown. Here, we report that adult-born neurons in crayfish can be derived from hemocytes. Following adoptive transfer of 5-ethynyl-2′-deoxyuridine (EdU)-labeled hemocytes, labeled cells populate the neurogenic niche containing the first-generation neuronal precursors. Seven weeks after adoptive transfer, EdU-labeled cells are located in brain clusters 9 and 10 (where adult-born neurons differentiate) and express appropriate neurotransmitters. Moreover, the number of cells composing the neurogenic niche in crayfish is tightly correlated with total hemocyte counts (THCs) and can be manipulated by raising or lowering THC. These studies identify hemocytes as a source of adult-born neurons in crayfish and demonstrate that the immune system is a key contributor to adult neurogenesis.

  • 23.
    Berggren, Olof
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Hagberg, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Alexsson, Andrei
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Weber, Gert
    Ernst Moritz Arndt Univ Greifswald, Inst Biochem, Dept Mol Struct Biol, Greifswald, Germany..
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Eloranta, Maija-Leena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Plasmacytoid dendritic cells and RNA-containing immune complexes drive expansion of peripheral B cell subsets with an SLE-like phenotype2017Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 8, artikel-id e0183946Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Hyperactive B cells and a continuous interferon (IFN)-alpha production by plasmacytoid dendritic cells (pDCs) play a key role in systemic lupus erythematosus (SLE). We asked whether the interaction between B cells and pDCs stimulated with RNA-containing immune complexes affects peripheral B cell subsets. Methods B cells and pDCs were isolated from blood of healthy individuals and stimulated with immune complexes consisting of SLE-IgG and U1snRNP (RNA-IC). Expression of cell surface molecules as well as IL-6 and IL-10 production were determined by flow cytometry and immunoassays. Gene expression profiles were determined by a NanoString nCounter expression array. Results We found a remarkable increase of double negative CD27-IgD-B cells, from 7% within fresh CD19+B cells to 37% in the RNA-IC-stimulated co-cultures of B cells and pDCs, comparable to the frequency of double negative B cells in SLE patients. Gene expression analysis of the double negative CD27-IgD -and the CD27 + IgD-memory B cells revealed that twenty-one genes were differentially expressed between the two B cell subsets (>= 2-fold, p< 0.001). The, IL21R, IL4R, CCL4, CCL3, CD83 and the IKAROS Family Zinc Finger 2 (IKZ2) showed higher expression in the double negative CD27-IgD-B cells. Conclusion The interactions between B cells and pDCs together with RNA-containing IC led to an expansion of B cells with similar phenotype as seen in SLE, suggesting that the pDC-B cell crosstalk contributes to the autoimmune feed-forward loop in SLE.

  • 24.
    Bergström, Joakim J. E.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Heyman, Birgitta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Mice Immunized With IgG Anti-Sheep Red Blood Cells (SRBC) Together With SRBC Have a Suppressed Anti-SRBC Antibody Response but Generate Germinal Centers and Anti-IgG Antibodies in Response to the Passively Administered IgG2017Ingår i: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 8, artikel-id 911Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Antigen-specific IgG antibodies, passively administered together with large particulate antigens such as erythrocytes, can completely suppress the antigen-specific antibody response. The mechanism behind has been elusive. Herein, we made the surprising observation that mice immunized with IgG anti-sheep red blood cells (SRBC) and SRBC, in spite of a severely suppressed anti-SRBC response, have a strong germinal center (GC) response. This occurred regardless of whether the passively administered IgG was of the same allotype as that of the recipient or not. Six days after immunization, the GC size and the number of GC B cells were higher in mice immunized with SRBC alone than in mice immunized with IgG and SRBC, but at the other time points these parameters were similar. GCs in the IgG-groups had a slight shift toward dark zone B cells 6 days after immunization and toward light zone B cells 10 days after immunization. The proportions of T follicular helper cells (TFH) and T follicular regulatory cells (TFR) were similar in the two groups. Interestingly, mice immunized with allogeneic IgG anti-SRBC together with SRBC mounted a vigorous antibody response against the passively administered suppressive IgG. Thus, although their anti-SRBC response was almost completely suppressed, an antibody response against allogeneic, and probably also syngeneic, IgG developed. This most likely explains the development of GCs in the absence of an anti-SRBC antibody response.

  • 25.
    Bhandage, Amol K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysiologi.
    Glutamate and GABA signalling components in the human brain and in immune cells2016Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Glutamate and γ-aminobutyric acid (GABA) are the principal excitatory and inhibitory neurotransmitters in the central nervous system (CNS). They both can activate their ionotropic and metabotropic receptors. Glutamate activates ionotropic glutamate receptors (iGlu - AMPA, kainate and NMDA receptors) and GABA activates GABA-A receptors which are modulated by many types of drugs and substances including alcohol. Using real time quantitative polymerase chain reaction, I have shown that iGlu and/or GABA-A receptor subunits were expressed in the hippocampus dentate gyrus (HDG), orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DL-PFC), central amygdala (CeA), caudate and putamen of the human brain and their expression was altered by chronic excessive alcohol consumption. It indicates that excitatory and inhibitory neurotransmission may have been altered in the brain of human alcoholics. It is possible that changes in one type of neurotransmitter system may drive changes in another. These brain regions also play a role in brain reward system. Any changes in them may lead to changes in the normal brain functions.

    Apart from the CNS, glutamate and GABA are also present in the blood and can be synthesised by pancreatic islet cells and immune cells. They may act as immunomodulators of circulating immune cells and can affect immune function through glutamate and GABA receptors. I found that T cells from human, rat and mouse lymph nodes expressed the mRNAs and proteins for specific GABA-A receptor subunits. GABA-evoked transient and tonic currents recorded using the patch clamp technique demonstrate the functional GABA-A channel in T cells. Furthermore, the mRNAs for specific iGlu, GABA-A and GABA-B receptor subunits and chloride cotransporters were detected in peripheral blood mononuclear cells (PBMCs) from men, non-pregnant women, healthy and depressed pregnant women. The results indicate that the expression of iGlu, GABA-A and GABA-B receptors is related to gender, pregnancy and mental health and support the notion that glutamate and GABA receptors may modulate immune function. Intra- and interspecies variability exists in the expression and it is further influenced by physiological conditions.

    Delarbeten
    1. Selective increases of AMPA, NMDA, and kainate receptor subunit mRNAs in the hippocampus and orbitofrontal cortex but not in prefrontal cortex of human alcoholics
    Öppna denna publikation i ny flik eller fönster >>Selective increases of AMPA, NMDA, and kainate receptor subunit mRNAs in the hippocampus and orbitofrontal cortex but not in prefrontal cortex of human alcoholics
    Visa övriga...
    2014 (Engelska)Ingår i: Frontiers in Cellular Neuroscience, ISSN 1662-5102, E-ISSN 1662-5102, Vol. 8, s. 11-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Glutamate is the main excitatory transmitter in the human brain. Drugs that affect the glutamatergic signaling will alter neuronal excitability. Ethanol inhibits glutamate receptors. We examined the expression level of glutamate receptor subunit mRNAs in human post-mortem samples from alcoholics and compared the results to brain samples from control subjects. RNA from hippocampal dentate gyrus (HP-DG), orbitofrontal cortex (OFC), and dorso-lateral prefrontal cortex (DL-PFC) samples from 21 controls and 19 individuals with chronic alcohol dependence were included in the study. Total RNA was assayed using quantitative RT-PCR. Out of the 16 glutamate receptor subunits, mRNAs encoding two AMPA [2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid] receptor subunits GluA2 and GluA3; three kainate receptor subunits GluK2, GluK3 and GluK5 and five NMDA (N-methyl-D-aspartate) receptor subunits GluN1, GluN2A, GluN2C, GluN2D, and GluN3A were significantly increased in the HP-DG region in alcoholics. In the OFC, mRNA encoding the NMDA receptor subunit GluN3A was increased, whereas in the DL-PFC, no differences in mRNA levels were observed. Our laboratory has previously shown that the expression of genes encoding inhibitory GABA-A receptors is altered in the HP-DG and OFC of alcoholics (Jin et al., 2011). Whether the changes in one neurotransmitter system drives changes in the other or if they change independently is currently not known. The results demonstrate that excessive long-term alcohol consumption is associated with altered expression of genes encoding glutamate receptors in a brain region-specific manner. It is an intriguing possibility that genetic predisposition to alcoholism may contribute to these gene expression changes.

    Nationell ämneskategori
    Fysiologi Neurovetenskaper
    Identifikatorer
    urn:nbn:se:uu:diva-219489 (URN)10.3389/fncel.2014.00011 (DOI)000331053400001 ()24523671 (PubMedID)
    Tillgänglig från: 2014-03-03 Skapad: 2014-03-03 Senast uppdaterad: 2018-01-11Bibliografiskt granskad
    2. Expression of specific ionotropic glutamate and GABA-A receptor subunits is decreased in central amygdala of alcoholics
    Öppna denna publikation i ny flik eller fönster >>Expression of specific ionotropic glutamate and GABA-A receptor subunits is decreased in central amygdala of alcoholics
    Visa övriga...
    2014 (Engelska)Ingår i: Frontiers in Cellular Neuroscience, ISSN 1662-5102, E-ISSN 1662-5102, Vol. 8, s. 288-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The central amygdala (CeA) has a role for mediating fear and anxiety responses. It is also involved in emotional imbalance caused by alcohol abuse and dependence and in regulating relapse to alcohol abuse. Growing evidences suggest that excitatory glutamatergic and inhibitory gamma-aminobutyric acid-ergic (GABAergic) transmissions in the CeA are affected by chronic alcohol exposure. Human post-mortem CeA samples from male alcoholics (n = 9) and matched controls (n = 9) were assayed for the expression level of ionotropic glutamate and GABA-A receptors subunit mRNAs using quantitative real-time reverse transcription-PCB (RT-qPCR). Our data revealed that out of the 16 ionotropic glutamate receptor subunits, mRNAs encoding two AMPA P-amino-3-(3-hydroxy-5-methyl-isoxazol-4-y1)propanoic acid] receptor subunits GluA1 and GluA4; one kainate receptor subunit GluK2; one NMDA (N-methyl-D-aspartate) receptor subunit GluN2D and one delta receptor subunit GluD2 were significantly decreased in the CeA of alcoholics. In contrast, of the 19 GABA-A receptor subunits, only the mRNA encoding the a2 subunit was significantly down-regulated in the CeA of the alcoholics as compared with control subjects. Our findings imply that the down-regulation of specific ionotropic glutamate and GABA-A receptor subunits in the CeA of alcoholics may represent one of the molecular substrates underlying the new balance between excitatory and inhibitory neurotransmission in alcohol dependence.

    Nationell ämneskategori
    Neurovetenskaper
    Identifikatorer
    urn:nbn:se:uu:diva-239603 (URN)10.3389/fncel.2014.00288 (DOI)000344465400002 ()
    Tillgänglig från: 2014-12-30 Skapad: 2014-12-29 Senast uppdaterad: 2018-01-11Bibliografiskt granskad
    3.
    Posten kunde inte hittas. Det kan bero på att posten inte längre är tillgänglig eller att du har råkat ange ett felaktigt id i adressfältet.
    4. Different subtypes of GABA-A receptors are expressed in human, mouse and rat T lymphocytes
    Öppna denna publikation i ny flik eller fönster >>Different subtypes of GABA-A receptors are expressed in human, mouse and rat T lymphocytes
    2012 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 8, s. e42959-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    γ-aminobutyric acid (GABA) is the most prominent neuroinhibitory transmitter in the brain, where it activates neuronalGABA-A receptors (GABA-A channels) located at synapses and outside of synapses. The GABA-A receptors are primarytargets of many clinically useful drugs. In recent years, GABA has been shown to act as an immunomodulatory molecule. Wehave examined in human, mouse and rat CD4+ and CD8+ T cells which subunit isoforms of the GABA-A channels areexpressed. The channel physiology and drug specificity is dictated by the GABA-A receptor subtype, which in turn isdetermined by the subunit isoforms that make the channel. There were 5, 8 and 13 different GABA-A subunit isoformsidentified in human, mouse and rat CD4+ and CD8+ T cells, respectively. Importantly, the γ2 subunit that imposesbenzodiazepine sensitivity on the GABA-A receptors, was only detected in the mouse T cells. Immunoblots andimmunocytochemistry showed abundant GABA-A channel proteins in the T cells from all three species. GABA-activatedwhole-cell transient and tonic currents were recorded. The currents were inhibited by picrotoxin, SR95531 and bicuculline,antagonists of GABA-A channels. Clearly, in both humans and rodents T cells, functional GABA-A channels are expressed butthe subtypes vary. It is important to bear in mind the interspecies difference when selecting the appropriate animal modelsto study the physiological role and pharmacological properties of GABA-A channels in CD4+ and CD8+ T cells and whenselecting drugs aimed at modulating the human T cells function.

    Nationell ämneskategori
    Neurovetenskaper
    Identifikatorer
    urn:nbn:se:uu:diva-172532 (URN)10.1371/journal.pone.0042959 (DOI)000307789700016 ()
    Tillgänglig från: 2012-04-11 Skapad: 2012-04-11 Senast uppdaterad: 2018-01-12Bibliografiskt granskad
    5. Expression of GABA receptors subunits in peripheral blood mononuclear cells is gender dependent, altered in pregnancy and modified by mental health
    Öppna denna publikation i ny flik eller fönster >>Expression of GABA receptors subunits in peripheral blood mononuclear cells is gender dependent, altered in pregnancy and modified by mental health
    Visa övriga...
    2015 (Engelska)Ingår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 213, nr 3, s. 575-585Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    AIM: The concept of nerve-driven immunity recognizes a link between the nervous and the immune system. γ-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain and receptors activated by GABA can be expressed by immune cells. Here we examined if the expression of GABA receptors and chloride transporters in human peripheral mononuclear cells (PBMCs) were influenced by gender, pregnancy or mental health.

    METHODS: We used RT-qPCR to determine the mRNA expression level in men (n=16), non-pregnant women (n=19), healthy pregnant women (n=27) and depressed pregnant women (n=15).

    RESULTS: The ρ2 subunit had the most prominent expression level of the GABA-A receptor subunits in all samples. The δ and ρ2 subunits were up-regulated by pregnancy whereas the ε subunit was more frequently expressed in healthy pregnant women than non-pregnant women who, in-turn, commonly expressed the α6 and the γ2 subunits. The β1 and ε subunits expression was altered by depression in pregnant women. The GABA-B1 receptor was up-regulated by depression in pregnant women while the transporters NKCC1 and KCC4 were down-regulated by pregnancy. The changes recorded in the mRNA expression levels imply participation of GABA receptors in establishing and maintaining tolerance in pregnancy. Importantly, the correlation of mental health with the expression of specific receptor subunits reveals a connection between the immune cells and the brain. Biomarkers for mental health may be identified in PBMCs.

    CONCLUSION: The results demonstrate the impact gender, pregnancy and mental health have on expression of GABA receptors plus chloride transporters expressed in human PBMCs.

    Nationell ämneskategori
    Fysiologi
    Identifikatorer
    urn:nbn:se:uu:diva-240372 (URN)10.1111/apha.12440 (DOI)000348531600007 ()25529063 (PubMedID)
    Tillgänglig från: 2015-01-07 Skapad: 2015-01-07 Senast uppdaterad: 2018-01-11
    6. AMPA, NMDA and kainate glutamate receptor subunits are expressed in human peripheral blood mononuclear cells (PBMCs) where the expression of GluK4 is altered by pregnancy and GluN2D by depression in pregnant women
    Öppna denna publikation i ny flik eller fönster >>AMPA, NMDA and kainate glutamate receptor subunits are expressed in human peripheral blood mononuclear cells (PBMCs) where the expression of GluK4 is altered by pregnancy and GluN2D by depression in pregnant women
    Visa övriga...
    2017 (Engelska)Ingår i: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 305, s. 51-58Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The amino acid glutamate opens cation permeable ion channels, the iGlu receptors. These ion channels are abundantly expressed in the mammalian brain where glutamate is the main excitatory neurotransmitter. The neurotransmitters and their receptors are being increasingly detected in the cells of immune system. Here we examined the expression of the 18 known subunits of the iGlu receptors families; alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate, N-methyl-D-aspartate (NMDA) and delta in human peripheral blood mononuclear cells (PBMCs). We compared the expression of the subunits between four groups: men, non-pregnant women, healthy pregnant women and depressed pregnant women.

    Out of 18 subunits of the iGlu receptors, mRNAs for 11 subunits were detected in PBMCs from men and nonpregnant women; AMPA: GluA3, GluA4, kainate: GluK2, GluK4, GluK5, NMDA: GluN1, GluN2C, GluN2D, GluN3A, GluN3B, and delta: GluD1. In the healthy and the depressed pregnant women, in addition, the delta GluD2 subunit was identified. The mRNAs for GluK4, GluK5, GluN2C and GluN2D were expressed at a higher level than other subunits. Gender, pregnancy or depression during pregnancy altered the expression of GluA3, GluK4, GluN2D, GluN3B and GluD1 iGlu subunit mRNAs. The greatest changes recorded were the lower GluA3 and GluK4 mRNA levels in pregnant women and the higher GluN2D mRNA level in healthy but not in depressed pregnant women as compared to non-pregnant individuals. Using subunit specific antibodies, the GluK4, GluK5, GluNl, GluN2C and GluN2D subunit proteins were identified in the PBMCs. The results show expression of specific iGlu receptor subunit in the PBMCs and support the idea of physiology-driven changes of iGlu receptors subtypes in the immune cells.

    Nyckelord
    Glutamate, iGluR subunits, Immune cells, Pregnancy, Depression, Physiology-driven changes
    Nationell ämneskategori
    Medicin och hälsovetenskap Neurovetenskaper
    Identifikatorer
    urn:nbn:se:uu:diva-282410 (URN)10.1016/j.jneuroim.2017.01.013 (DOI)000397694200009 ()28284346 (PubMedID)
    Forskningsfinansiär
    Vetenskapsrådet, 521-2012-1789
    Tillgänglig från: 2016-04-05 Skapad: 2016-04-05 Senast uppdaterad: 2018-01-10Bibliografiskt granskad
  • 26.
    Biasoli, Deborah
    et al.
    Anim Hlth Trust, Newmarket, Suffolk, England.
    Compston-Garnett, Lara
    Anim Hlth Trust, Newmarket, Suffolk, England.
    Ricketts, Sally L.
    Anim Hlth Trust, Newmarket, Suffolk, England.
    Birand, Zeynep
    Anim Hlth Trust, Newmarket, Suffolk, England.
    Courtay-Cahen, Celine
    Anim Hlth Trust, Newmarket, Suffolk, England.
    Fineberg, Elena
    Anim Hlth Trust, Newmarket, Suffolk, England.
    Arendt, Maja Louise
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Boerkamp, Kim
    Univ Utrecht, Dept Clin Sci Compan Anim, Utrecht, Netherlands;Med Evaluat Board, Utrecht, Netherlands.
    Melin, Malin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Koltookian, Michele
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
    Murphy, Sue
    Anim Hlth Trust, Newmarket, Suffolk, England;Univ Edinburgh, Royal Dick Sch Vet Studies, Edinburgh, Midlothian, Scotland.
    Rutteman, Gerard
    Univ Utrecht, Dept Clin Sci Compan Anim, Utrecht, Netherlands;Vet Specialist Ctr Wagenrenk, Wageningen, Netherlands.
    Lindblad-Toh, Kerstin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
    Starkey, Mike
    Anim Hlth Trust, Newmarket, Suffolk, England.
    A synonymous germline variant in a gene encoding a cell adhesion molecule is associated with cutaneous mast cell tumour development in Labrador and Golden Retrievers2019Ingår i: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 15, nr 3, artikel-id e1007967Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mast cell tumours are the most common type of skin cancer in dogs, representing a significant concern in canine health. The molecular pathogenesis is largely unknown, but breed-predisposition for mast cell tumour development suggests the involvement of inherited genetic risk factors in some breeds. In this study, we aimed to identify germline risk factors associated with the development of mast cell tumours in Labrador Retrievers, a breed with an elevated risk of mast cell tumour development. Using a methodological approach that combined a genome-wide association study, targeted next generation sequencing, and TaqMan genotyping, we identified a synonymous variant in the DSCAM gene on canine chromosome 31 that is associated with mast cell tumours in Labrador Retrievers. DSCAM encodes a cell-adhesion molecule. We showed that the variant has no effect on the DSCAM mRNA level but is associated with a significant reduction in the level of the DSCAM protein, suggesting that the variant affects the dynamics of DSCAM mRNA translation. Furthermore, we showed that the variant is also associated with mast cell tumours in Golden Retrievers, a breed that is closely related to Labrador Retrievers and that also has a predilection for mast cell tumour development. The variant is common in both Labradors and Golden Retrievers and consequently is likely to be a significant genetic contributor to the increased susceptibility of both breeds to develop mast cell tumours. The results presented here not only represent an important contribution to the understanding of mast cell tumour development in dogs, as they highlight the role of cell adhesion in mast cell tumour tumourigenesis, but they also emphasise the potential importance of the effects of synonymous variants in complex diseases such as cancer. Author summary The combination of various genetic and environmental risk factors makes the understanding of the molecular circuitry behind complex diseases, like cancer, a major challenge. The homogeneous nature of pedigree dog breed genomes makes these dogs ideal for the identification of both simple disease-causing genetic variants and genetic risk factors for complex diseases. Mast cell tumours are the most common type of canine skin cancer, and one of the most common cancers affecting dogs of most breeds. Several breeds, including Labrador Retrievers (which represent one of the most popular dog breeds), have an elevated risk of mast cell tumour development. Here, by using a methodological approach that combined different techniques, we identified a common inherited synonymous variant, that predisposes Labrador Retrievers to mast cell tumour development. Interestingly, we showed that this variant, despite its synonymous nature, appears to have an effect on translation dynamics as it is associated with reduced levels of DSCAM, a cell adhesion molecule. The results presented here reveal dysregulation of cell adhesion to be an important factor in mast cell tumour pathogenesis, and also highlight the important role that synonymous variants can play in complex diseases.

  • 27.
    Biglarnia, Ali-Reza
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Nilsson, Kristina Ekdahl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Nilsson, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Complement Interception Across Humoral Incompatibility in Solid Organ Transplantation: A Clinical Perspective2015Ingår i: IMMUNE RESPONSES TO BIOSURFACES: MECHANISMS AND THERAPEUTIC INTERVENTIONS, 2015, s. 211-233Konferensbidrag (Refereegranskat)
    Abstract [en]

    The humoral barrier in transplant biology is the result of preformed donor-specific antibodies (DSAs), directed either against human leukocyte antigens (HLA) or non-HLA antigens such as blood group (ABO) molecules. The term "sensitization" applies to patients carrying these antibodies. Transplantation is widely accepted as a life-saving opportunity for patients with terminal end-organ disease. However, in sensitized patients, transplant outcome is hampered by antibody-mediated rejection (AMR) as a consequence of DSA exposure. Furthermore, sensitized patients have limited access to "matched" organs from the both living and deceased donor pool. Considering the crucial role of the complement system in the pathophysiology of AMR and the availability of complement intervention therapeutics, there is a growing interest in complement-targeting strategies. This review highlights the emerging importance of monitoring and modulation of the complement system in the context of enabling transplantation across humoral incompatibility in sensitized recipients with preformed anti-HLA or natural anti-ABO antibodies. It also discusses the significance of the complement system in the induction of accommodation and further emphasizes current and future perspectives of novel complement therapeutics.

  • 28. Bonnedahl, Jonas
    et al.
    Hernandez, Jorge
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi och infektionsmedicin.
    Stedt, Johan
    Waldenstrom, Jonas
    Olsen, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Drobni, Mirva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi och infektionsmedicin.
    Extended-Spectrum beta-Lactamases in Escherichia coli and Klebsiella pneumoniae in Gulls, Alaska, USA2014Ingår i: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 20, nr 5, s. 897-899Artikel i tidskrift (Refereegranskat)
  • 29.
    Bremer, Hanna D.
    et al.
    Swedish Univ Agr Sci SLU, Dept Clin Sci, Box 7054, SE-75007 Uppsala, Sweden..
    Lattwein, Erik
    Euroimmun AG, Lubeck, Germany..
    Renneker, Stefanie
    Euroimmun AG, Lubeck, Germany..
    Lilliehook, Inger
    Swedish Univ Agr Sci, Univ Anim Hosp, Clin Pathol Lab, Uppsala, Sweden..
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Hansson-Hamlin, Helene
    Swedish Univ Agr Sci SLU, Dept Clin Sci, Box 7054, SE-75007 Uppsala, Sweden..
    Identification of specific antinuclear antibodies in dogs using a line immunoassay and enzyme-linked immunosorbent assay2015Ingår i: Veterinary Immunology and Immunopathology, ISSN 0165-2427, E-ISSN 1873-2534, Vol. 168, nr 3-4, s. 233-241Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Circulating antinuclear antibodies (ANA) are commonly present in the systemic autoimmune disease Systemic Lupus Erythematosus (SLE) and in other systemic rheumatic diseases, in humans as well as in dogs. The indirect immunofluorescence (IIF)-ANA test is the standard method for detecting ANA. Further testing for specific ANA with immunoblot techniques or ELISAs is routinely performed in humans to aid in the diagnosis and monitoring of disease. Several specific ANA identified in humans have been identified also in suspected canine SLE but, in contrast to humans, investigation of autoantibodies in canine SLE is mainly restricted to the IIF-ANA test. Our aim was to identify both known and novel specific ANA in dogs and to investigate if different IIF-ANA patterns are associated with different specific ANA in dogs. Sera from 240 dogs with suspicion of autoimmune disease (210 IIF-ANA positive (ANA(pos)) and 30 IIF-ANA negative (ANA(neg))) as well as sera from 27 healthy controls were included. The samples were analysed with a line immunoassay, LIA (Euroline ANA Profile 5, Euroimmun, Lubeck, Germany) and four different ELISAs (Euroimmun). The ANA(pos) dogs were divided in two groups depending on the type of IIF-ANA pattern. Of the 210 ANA(pos) samples 68 were classified as ANA homogenous (ANA(H)) and 141 as ANA speckled (ANA(S)), one sample was not possible to classify. Dogs in the ANA(H) group had, compared to the other groups, most frequently high levels of anti-double stranded deoxyribonucleic acid (dsDNA) and anti-nucleosome ANA. Anti-dsDNA antibodies were confirmed in some dogs with the Crithidia luciliae indirect immunofluorescence test (CLIFT).The frequency of ANA(H) dogs with values above those observed in the healthy group was significantly higher compared to ANA(S) dogs for anti-dsDNA, anti-nucleosome, and anti-histone reactivity. Dogs in the ANA(S) group had, compared to the other groups, most frequently high levels of anti-ribonucleoproteins (RNP) and/or anti-Smith (Sm) antibodies. Reactivity against Sjogren's syndrome related antigens (SS)-A (including the Ro-60 and Ro-52 subcomponents), SS-B, histidyl tRNA synthetase (Jo-1), topoisomerase I antigen (Scl-70), polymyositis-scleroderma antigen (PM-Scl) and proliferating cell nuclear antigen (PCNA) was also noted in individual dogs. In conclusion, by using a commercial LIA and different ELISAs originally developed for detection of human ANA, we identified several specific ANA in serum samples from dogs sampled for IIF-ANA testing. Further, we found that the types of IIF-ANA pattern were associated with reactivity against some particular nuclear antigens.

  • 30.
    Brink, Mikael
    et al.
    Umea Univ, Dept Publ Hlth & Clin Med, Div Rheumatol, SE-90185 Umea, Sweden..
    Hansson, Monika
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Mathsson-Alm, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Thermo Fisher Sci, Uppsala, Sweden..
    Wijayatunga, Priyantha
    Umea Univ, Dept Stat, S-90187 Umea, Sweden..
    Verheul, Marije K.
    Leiden Univ, Med Ctr, Dept Rheumatol, Leiden, Netherlands..
    Trouw, Leendert A.
    Leiden Univ, Med Ctr, Dept Rheumatol, Leiden, Netherlands..
    Holmdahl, Rikard
    Karolinska Inst, Med Inflammat Res Med Biophys & Biochem, Stockholm, Sweden..
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Klareskog, Lars
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Rantapaa-Dahlqvist, Solbritt
    Umea Univ, Dept Publ Hlth & Clin Med, Div Rheumatol, SE-90185 Umea, Sweden..
    Rheumatoid factor isotypes in relation to antibodies against citrullinated peptides and carbamylated proteins before the onset of rheumatoid arthritis2016Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 18, artikel-id 43Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The presence of rheumatoid factor (RF), anti-carbamylated protein antibodies (anti-CarP) and antibodies against citrullinated protein and peptides (ACPA) precedes the onset of symptoms of rheumatoid arthritis (RA) by several years. Relationships between the development of these antibodies are not obvious. Methods: Three isotypes [immunoglobulin A (IgA), IgG and IgM) of RF were analysed in 321 pre-symptomatic individuals who provided 598 samples collected a median of 6.2 (interquartile range 7.2) years before the onset of symptoms, and in 492 population control subjects. All samples were donated to the Biobank of Northern Sweden. RF isotypes were analysed using the EliA system (Phadia GmbH, Freiburg, Germany) with 96 % specificity according to receiver operating characteristic curves. Ten ACPA specificities were analysed using the ImmunoCAP ISAC system, and anti-CCP2 and anti-CarP antibodies were evaluated using enzyme-linked immunosorbent assays. Results: The frequencies of RF isotypes in pre-symptomatic individuals were significantly increased compared with control subjects (p < 0.0001). In samples collected >= 15 years before the onset of symptoms, the IgA-RF isotype was significantly more prevalent than the most frequent ACPAs. Combinations of IgM- and IgA-RF isotypes with ACPA specificities [a-enolase (CEP-1/Eno(5-21))], fibrinogen (Fib)beta(36-52), Fiba(580-600), filaggrin (CCP-1/Fil(307-324)) and anti-CCP2 antibodies were associated with a significantly shorter time to onset of symptoms (p < 0.001-0.05). Using conditional inference tree analysis, anti-CCP2 in combination with anti-filaggrin antibodies gave the highest probability, 97.5 %, for disease development. Conclusions: RF isotypes predicted the development of RA, particularly in combination with ACPA, anti-CCP2 or anti-CarP antibodies. The highest probability for disease development was the presence of anti-CCP2 and anti-filaggrin antibodies.

  • 31.
    Bösl, Korbinian
    et al.
    Norwegian Univ Sci & Technol, Ctr Mol Inflammat Res, Trondheim, Norway;Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway.
    Ianevski, Aleksandr
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway.
    Than, Thoa T.
    Inst Pasteur Korea, Seongnam, South Korea.
    Andersen, Petter I.
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway.
    Kuivanen, Suvi
    Univ Helsinki, Dept Virol, Helsinki, Finland.
    Teppor, Mona
    Univ Tartu, Inst Technol, Tartu, Estonia.
    Zusinaite, Eva
    Univ Tartu, Inst Technol, Tartu, Estonia.
    Dumpis, Uga
    Pauls Stradins Clin Univ Hosp, Riga, Latvia.
    Vitkauskiene, Astra
    Lithuanian Univ Hlth Sci, Dept Lab Med, Kaunas, Lithuania.
    Cox, Rebecca J.
    Univ Bergen, Dept Clin Sci, Influenza Ctr, Bergen, Norway.
    Kallio-Kokko, Hannimari
    Univ Helsinki, Dept Virol & Immunol, Helsinki Univ Hosp, Helsinki, Finland.
    Bergqvist, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin.
    Tenson, Tanel
    Univ Tartu, Inst Technol, Tartu, Estonia.
    Merits, Andres
    Univ Tartu, Inst Technol, Tartu, Estonia.
    Oksenych, Valentyn
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway.
    Björås, Magnar
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway.
    Anthonsen, Marit W.
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway.
    Shum, David
    Inst Pasteur Korea, Seongnam, South Korea.
    Kaarbö, Mari
    Oslo Univ Hosp, Dept Microbiol, Oslo, Norway.
    Vapalahti, Olli
    Univ Helsinki, Dept Vet Biosci, Helsinki, Finland.
    Windisch, Marc P.
    Inst Pasteur Korea, Seongnam, South Korea.
    Superti-Furga, Giulio
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria;Med Univ Vienna, Ctr Physiol & Pharmacol, Vienna, Austria.
    Snijder, Berend
    Swiss Fed Inst Technol, Inst Mol Syst Biol, Dept Biol, Zurich, Switzerland.
    Kainov, Denis
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway;Swiss Fed Inst Technol, Inst Mol Syst Biol, Dept Biol, Zurich, Switzerland.
    Kandasamy, Richard K.
    Norwegian Univ Sci & Technol, Ctr Mol Inflammat Res, Trondheim, Norway;Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway;Univ Oslo, Nord EMBL Partnership, Ctr Mol Med Norway NCMM, Oslo, Norway;Univ Massachusetts, Sch Med, Dept Med, Program Innate Immun,Div Infect Dis & Immunol, Worcester, MA 01655 USA.
    Common Nodes of Virus-Host Interaction Revealed Through an Integrated Network Analysis2019Ingår i: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 10, artikel-id 2186Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Viruses are one of the major causes of acute and chronic infectious diseases and thus a major contributor to the global burden of disease. Several studies have shown how viruses have evolved to hijack basic cellular pathways and evade innate immune response by modulating key host factors and signaling pathways. A collective view of these multiple studies could advance our understanding of virus-host interactions and provide new therapeutic perspectives for the treatment of viral diseases. Here, we performed an integrative meta-analysis to elucidate the 17 different host-virus interactomes. Network and bioinformatics analyses showed how viruses with small genomes efficiently achieve the maximal effect by targeting multifunctional and highly connected host proteins with a high occurrence of disordered regions. We also identified the core cellular process subnetworks that are targeted by all the viruses. Integration with functional RNA interference (RNAi) datasets showed that a large proportion of the targets are required for viral replication. Furthermore, we performed an interactome-informed drug re-purposing screen and identified novel activities for broad-spectrum antiviral agents against hepatitis C virus and human metapneumovirus. Altogether, these orthogonal datasets could serve as a platform for hypothesis generation and follow-up studies to broaden our understanding of the viral evasion landscape.

  • 32.
    Cerenius, Lage
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Jämförande fysiologi.
    Babu, Ramesh
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Jämförande fysiologi.
    Söderhäll, Kenneth
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Jämförande fysiologi.
    Jiravanichpaisal, Pikul
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Jämförande fysiologi.
    In vitro effects on bacterial growth of phenoloxidase reaction products2010Ingår i: Journal of Invertebrate Pathology, ISSN 0022-2011, E-ISSN 1096-0805, Vol. 103, nr 1, s. 21-23Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    An active phenoloxidase preparation from the freshwater crayfish Pacifastacus leniusculus exhibited a strong antibacterial effect in vitro on the bacteria Aeromonas hydrophila, Escherichia coli, Streptococcus pneumoniae whereas a weaker but still significant effect against Bacillus cereus, Pseudomonas aeruginosa and Staphylococcus aureus. In most cases reduction of bacterial growth was stronger when dopamine was used as substrate as compared to L-dopa. The effect on bacteria was abolished if no substrate was available for the phenoloxidase or in the presence of the phenoloxidase inhibitor phenylthiourea.

  • 33.
    Cerenius, Lage
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Jämförande fysiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi. Jämförande fysiologi.
    Bangyeekhun, Eakaphun
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Jämförande fysiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi. Jämförande fysiologi.
    Keyser, Pia
    Söderhäll, Irene
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Jämförande fysiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi. jämförande fysiologi.
    Söderhäll, Kenneth
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Jämförande fysiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi. jämförande fysiologi.
    Host prophenoloxidase expression in freshwater crayfish is linked to increased resistance to the crayfish plague fungus, Aphanomyces astaci.2003Ingår i: Cell Microbiol, ISSN 1462-5814, Vol. 5, nr 5, s. 353-7Artikel i tidskrift (Refereegranskat)
  • 34.
    Cerenius, Lage
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Jämförande fysiologi.
    Kawabata, Shun-ichiro
    Lee, Bok Luel
    Nonaka, Masaru
    Söderhäll, Kenneth
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Jämförande fysiologi.
    Proteolytic cascades and their involvement in invertebrate immunity2010Ingår i: TIBS -Trends in Biochemical Sciences. Regular ed., ISSN 0968-0004, E-ISSN 1362-4326, Vol. 35, nr 10, s. 575-583Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Bacteria and other potential pathogens are cleared rapidly from the body fluids of invertebrates by the immediate response of the innate immune system. Proteolytic cascades, following their initiation by pattern recognition proteins, control several such reactions, notably coagulation, melanisation, activation of the Toll receptor and complement-like reactions. However, there is considerable variation among invertebrates and these cascades, although widespread, are not present in all phyla. In recent years, significant progress has been made in identifying and characterizing these cascades in insects. Notably, recent work has identified several connections and shared principles among the different pathways, suggesting that cross-talk between them may be common.

  • 35.
    Cerenius, Lage
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Jämförande fysiologi.
    Kawabata, Shun-ichiro
    Kyushu University, Fukuoka, Japan.
    Söderhäll, Kenneth
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Jämförande fysiologi.
    Biological and Immunological Aspects of Innate Defence Mechanisms Activated by (1,3)- β -Glucans and Related Polysaccharides in Invertebrates2009Ingår i: Chemistry, Biochemistry and Biology of (1-›3)-β-Glucans and Related Polysaccharides. / [ed] Antony Bacic, Geoffrey B. Fincher & Bruce A. Stone, Burlington, MA: Academic Press , 2009, s. 563-577Kapitel i bok, del av antologi (Övrigt vetenskapligt)
    Abstract [en]

    (1,3)- β -glucans are powerful stimulants of a wide variety of innate defence reactions in invertebrates. These polysaccharides exert a great influence on reactions such as induction of antimicrobial peptides, cellular defence such as encapsulation and phagocytosis, and on the melanization and coagulation cascades. In most cases, these reactions set up an effective defence against microorganisms containing (1,3)- β -glucans or (1,3;1,6)- β -glucans in their outer structures (i.e. mainly fungi and oomycetes).

     

  • 36.
    Cerenius, Lage
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Jämförande fysiologi.
    Söderhäll, Kenneth
    Arthropoda:: Pattern recognition proteins in crustacean immunity2018Ingår i: Advances in Comparative Immunology, Springer, 2018Kapitel i bok, del av antologi (Övrigt vetenskapligt)
  • 37.
    Cerenius, Lage
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Jämförande fysiologi.
    Söderhäll, Kenneth
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Jämförande fysiologi.
    Coagulation in invertebrates2011Ingår i: Journal of Innate Immunity, ISSN 1662-811X, Vol. 3, nr 1, s. 3-8Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    In most animals there is a need to quickly prevent the loss of blood or equivalent fluids through inflicted injuries. In invertebrates with an open circulatory system (and sometimes a hydroskeleton as well) these losses may otherwise soon be fatal. Also, there is a need to prevent microbes that have gained access to the body through the wound from disseminating throughout the open circulatory system. Therefore, many invertebrates possess a coagulation system to prevent such accidents from having too serious consequences. In this review we discuss recent developments in a few animals - mainly arthropods - where more detailed data are available. It is likely, however, that corresponding systems are present in most phyla, but this is still unchartered territory.

  • 38. Cui, Yue
    et al.
    Dahlin, Joakim S.
    Feinstein, Ricardo
    Bankova, Lora G.
    Xing, Wei
    Shin, Kichul
    Gurish, Michael F.
    Hallgren, Jenny
    Mouse Mast Cell Protease-6 and MHC Are Involved in the Development of Experimental Asthma2014Ingår i: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 193, nr 10, s. 4783-4789Artikel i tidskrift (Refereegranskat)
  • 39.
    Dahlin, Joakim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Mast Cell Progenitor Trafficking in Allergic Airway Inflammation2013Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Mast cell progenitors originate from the bone marrow and migrate to the lungs via the blood. During maturation, these cells acquire granules that contain a potent array of bronchoconstrictive mediators. The number of pulmonary mast cells is augmented in asthmatic patients and in mice with allergic airway inflammation, possibly contributing to airway hyperreactivity. An increase in mast cells is likely due to an increased recruitment of committed mast cell progenitors from the blood. However, until now a committed mast cell progenitor population has not been found in adult peripheral blood. We isolated Lin- c-kithi ST2+ integrin β7hi CD16/32hi progenitors from murine blood and showed that these cells were committed to the mast cell lineage. Based on the expression of FcεRI, these cells were less mature in Th1-prone C57BL/6 mice than in Th2-prone BALB/c mice.

    Asthma is associated with elevated levels of IgE. Upon exposure to allergens, IgE immune complexes are formed. In a mouse model of allergic airway inflammation, we showed that intranasal administration of IgE immune complexes to antigen-sensitized mice resulted in an increased number of mast cell progenitors compared with antigen administration alone. The increase in mast cell progenitors was independent of the low-affinity IgE receptor CD23. Rather, signaling through the common FcRγ-chain was required to enhance the number of lung mast cell progenitors. Signaling through FcεRI was likely responsible for the increase. However a role for FcγRIV could not be excluded.

    CD11c+ cells, such as dendritic cells, are important for antigen sensitization. In a mouse model of allergic airway inflammation, these cells are also important for the development of airway hyperreactivity, eosinophilia and Th2 cytokine production in response to antigen challenge. We showed that CD11c+ cells are critical for the recruitment of lung mast cell progenitors and the subsequent increase in mast cells. These CD11c+ cells were needed for the upregulation of endothelial vascular cell adhesion molecule-1 (VCAM-1), which is a prerequisite for the antigen-induced recruitment of lung mast cell progenitors.

    Delarbeten
    1. IgE Immune Complexes Stimulate an Increase in Lung Mast Cell Progenitors in a Mouse Model of Allergic Airway Inflammation
    Öppna denna publikation i ny flik eller fönster >>IgE Immune Complexes Stimulate an Increase in Lung Mast Cell Progenitors in a Mouse Model of Allergic Airway Inflammation
    2011 (Engelska)Ingår i: PLoS One, ISSN 1932-6203, Vol. 6, nr 5, s. e20261-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Mast cell numbers and allergen specific IgE are increased in the lungs of patients with allergic asthma and this can be reproduced in mouse models. The increased number of mast cells is likely due to recruitment of mast cell progenitors that mature in situ. We hypothesized that formation of IgE immune complexes in the lungs of sensitized mice increase the migration of mast cell progenitors to this organ. To study this, a model of allergic airway inflammation where mice were immunized with ovalbumin (OVA) in alum twice followed by three daily intranasal challenges of either OVA coupled to trinitrophenyl (TNP) alone or as immune complexes with IgE-anti-TNP, was used. Mast cell progenitors were quantified by a limiting dilution assay. IgE immune complex challenge of sensitized mice elicited three times more mast cell progenitors per lung than challenge with the same dose of antigen alone. This dose of antigen challenge alone did not increase the levels of mast cell progenitors compared to unchallenged mice. IgE immune complex challenge of sensitized mice also enhanced the frequency of mast cell progenitors per 10 6 mononuclear cells by 2.1-fold. The enhancement of lung mast cell progenitors by IgE immune complex challenge was lost in FcR gamma deficient mice but not in CD23 deficient mice. Our data show that IgE immune complex challenge enhances the number of mast cell progenitors in the lung through activation of an Fc receptor associated with the FcR gamma chain. This most likely takes place via activation of Fc epsilon RI, although activation via Fc gamma RIV or a combination of the two receptors cannot be excluded. IgE immune complex-mediated enhancement of lung MCp numbers is a new reason to target IgE in therapies against allergic asthma.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-154525 (URN)10.1371/journal.pone.0020261 (DOI)000290771200055 ()21625525 (PubMedID)
    Tillgänglig från: 2011-06-07 Skapad: 2011-06-07 Senast uppdaterad: 2014-01-23Bibliografiskt granskad
    2. CD11c(+) Cells Are Required for Antigen-Induced Increase of Mast Cells in the Lung
    Öppna denna publikation i ny flik eller fönster >>CD11c(+) Cells Are Required for Antigen-Induced Increase of Mast Cells in the Lung
    Visa övriga...
    2012 (Engelska)Ingår i: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 189, nr 8, s. 3869-3877Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Patients with allergic asthma have more lung mast cells, which likely worsens the symptoms. In experimental asthma, CD11c(+) cells have to be present during the challenge phase for several features of allergic inflammation to occur. Whether CD11c(+) cells play a role for Ag-induced increases of lung mast cells is unknown. In this study, we used diphtheria toxin treatment of sensitized CD11c-diphtheria toxin receptor transgenic mice to deplete CD11c(+) cells. We demonstrate that recruitment of mast cell progenitors to the lung is substantially reduced when CD11c(+) cells are depleted during the challenge phase. This correlated with an impaired induction of endothelial VCAM-1 and led to a significantly reduced number of mature mast cells 1 wk after challenge. Collectively, these data suggest that Ag challenge stimulates CD11c(+) cells to produce cytokines and/or chemokines required for VCAM-1 upregulation on the lung endothelium, which in turn is crucial for the Ag-induced mast cell progenitor recruitment and the increase in mast cell numbers.

    Nationell ämneskategori
    Immunologi Immunologi inom det medicinska området
    Forskningsämne
    Immunologi
    Identifikatorer
    urn:nbn:se:uu:diva-184515 (URN)10.4049/jimmunol.1201200 (DOI)000309590900014 ()22972929 (PubMedID)
    Forskningsfinansiär
    Vetenskapsrådet
    Tillgänglig från: 2012-11-07 Skapad: 2012-11-07 Senast uppdaterad: 2018-01-12Bibliografiskt granskad
    3. Committed mast cell progenitors in mouse blood differ in maturity between Th1 and Th2 strains
    Öppna denna publikation i ny flik eller fönster >>Committed mast cell progenitors in mouse blood differ in maturity between Th1 and Th2 strains
    2013 (Engelska)Ingår i: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 68, nr 10, s. 1333-1337Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Mast cell progenitors (MCp) leave the bone marrow and migrate to peripheral tissues where they mature. Although the existence of committed MCp in adult mouse and human blood has been postulated, they have never been found. We have isolated a rare population of cells in adult mouse blood, committed to the mast cell lineage. These were identified as lineage c-kithi ST2+ integrin β7hi CD16/32hi cells. Moreover, a major difference in maturity of these cells based on FcεRI expression was observed between the Th2-prone BALB/c strain and the Th1-prone C57BL/6 strain (66% vs 25% FcεRI+, respectively). Therefore, the choice of mouse strain is critical when studying disease models such as experimental asthma where mast cells and their progenitors are involved.

    Nationell ämneskategori
    Immunologi Immunologi inom det medicinska området
    Identifikatorer
    urn:nbn:se:uu:diva-205507 (URN)10.1111/all.12223 (DOI)000326024300015 ()
    Tillgänglig från: 2013-09-02 Skapad: 2013-08-19 Senast uppdaterad: 2018-01-11Bibliografiskt granskad
  • 40.
    Dahlin, Joakim S
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Feinstein, Ricardo
    Statens veterinärmedicinska anstalt.
    Cui, Yue
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Heyman, Birgitta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Hallgren, Jenny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    CD11c(+) Cells Are Required for Antigen-Induced Increase of Mast Cells in the Lung2012Ingår i: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 189, nr 8, s. 3869-3877Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Patients with allergic asthma have more lung mast cells, which likely worsens the symptoms. In experimental asthma, CD11c(+) cells have to be present during the challenge phase for several features of allergic inflammation to occur. Whether CD11c(+) cells play a role for Ag-induced increases of lung mast cells is unknown. In this study, we used diphtheria toxin treatment of sensitized CD11c-diphtheria toxin receptor transgenic mice to deplete CD11c(+) cells. We demonstrate that recruitment of mast cell progenitors to the lung is substantially reduced when CD11c(+) cells are depleted during the challenge phase. This correlated with an impaired induction of endothelial VCAM-1 and led to a significantly reduced number of mature mast cells 1 wk after challenge. Collectively, these data suggest that Ag challenge stimulates CD11c(+) cells to produce cytokines and/or chemokines required for VCAM-1 upregulation on the lung endothelium, which in turn is crucial for the Ag-induced mast cell progenitor recruitment and the increase in mast cell numbers.

  • 41.
    Dahlin, Joakim S
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Heyman, Birgitta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Hallgren, Jenny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Committed mast cell progenitors in mouse blood differ in maturity between Th1 and Th2 strains2013Ingår i: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 68, nr 10, s. 1333-1337Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mast cell progenitors (MCp) leave the bone marrow and migrate to peripheral tissues where they mature. Although the existence of committed MCp in adult mouse and human blood has been postulated, they have never been found. We have isolated a rare population of cells in adult mouse blood, committed to the mast cell lineage. These were identified as lineage c-kithi ST2+ integrin β7hi CD16/32hi cells. Moreover, a major difference in maturity of these cells based on FcεRI expression was observed between the Th2-prone BALB/c strain and the Th1-prone C57BL/6 strain (66% vs 25% FcεRI+, respectively). Therefore, the choice of mouse strain is critical when studying disease models such as experimental asthma where mast cells and their progenitors are involved.

  • 42. Didinger, Chelsea
    et al.
    Eimes, John
    Lillie, Mette
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Waldman, Bruce
    Multiple major histocompatibility complex class I genes in Asian anurans: Ontogeny and phylogeny2017Ingår i: Developmental and Comparative Immunology, ISSN 0145-305X, E-ISSN 1879-0089, Vol. 70, s. 69-79Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Amphibians, as the first terrestrial vertebrates, offer a window into early major histocompatibility complex (MHC) evolution. We characterized the MHC class I of two Korean amphibians, the Asiatic toad (Bufo gargarizans) and the Japanese tree frog (Hyla japonica). We found at least four transcribed MHC class I (MHC I) loci, the highest number confirmed in any anuran to date. Furthermore, we identified MHC I transcripts in terrestrial adults, and possibly in aquatic larvae, of both species. We conducted a phylogenetic analysis based on MHC I sequence data and found that B. gargarizans and H. japonica cluster together in the superfamily Nobleobatrachia. We further identified three supertypes shared by the two species. Our results reveal substantial variation in the number of MHC I loci in anurans and suggest that certain supertypes have particular physiochemical properties that may confer pathogen resistance.

  • 43. Dubicke, Aurelija
    et al.
    Andersson, Peter
    Centini, Gabriele
    Fransson, Emma
    Karolinska Institutet.
    Anderson, Eva
    Bystrom, Birgitta
    Petraglia, Felice
    Sverremark, Eva
    Ekman-Ordeberg, Gunvor
    Altered Balance in Pro-Inflammatory and Anti-Inflammatory Cytokines in Preterm Cervical Ripening2009Konferensbidrag (Refereegranskat)
  • 44. Dubicke, Aurelija
    et al.
    Fransson, Emma
    Karolinska Instituet.
    Bystrom, Birgitta
    Yellon, Steven M.
    Ekman-Ordeberg, Gunvor
    Collagen Expression in Human Preterm Cervix.2014Konferensbidrag (Refereegranskat)
  • 45. Dubicke, Aurelija
    et al.
    Hell, Eva
    Fransson, Emma
    Karolinska Institutet.
    Ekman-Ordeberg, Gunvor
    Danielsson, Kristina Gemzell
    Marchini, Giovanna
    Circulating Cathelicidin Antimicrobial Peptide LL-37 Levels in Mothers and Preterm and Term Newborn Infants.2018Ingår i: Reproductive Investigation, Vol. 25, nr 1Artikel i tidskrift (Refereegranskat)
  • 46.
    Dubicke, Aurelija
    et al.
    Department of Woman and Child Health, Karolinska Institute. Stockholm, Sweden.
    Sverremark-Ekström, Eva
    Stockholms universitet.
    Fransson, Emma
    Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden.
    Centini, Gabriela
    Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, 53100 Siena, Ital.
    Andersson, Eva
    Department of Woman and Child Health, Karolinska Institute. Stockholm, Sweden.
    Byström, Birgitta
    Department of Woman and Child Health, Karolinska Institute. Stockholm, Sweden.
    Ekman-Ordeberga, Gunvor
    Department of Woman and Child Health, Karolinska Institute, Stockholm, Sweden.
    Malmström, Anders Malmström
    Department of Experimental Medical Science, University of Lund, 221 84 Lund, Sweden.
    Petraglia, Felice
    Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, 53100 Siena, Italy.
    Pro-inflammatory and anti-inflammatory cytokines in human preterm and term cervical ripening2010Ingår i: Journal of Reproductive Immunology, ISSN 0165-0378, E-ISSN 1872-7603, Vol. 84, nr 2, s. 176-185Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cervical ripening is necessary for successful delivery. Since cytokines are believed to be involved in this process, the aim of this study was to investigate possible changes in the mRNA and protein expression of pro-inflammatory cytokines (interleukin (IL)-1 alpha, IL-1 beta, IL-12, IL-18) and anti-inflammatory cytokines (IL-4, IL-10, IL-13)in the human cervix during pregnancy, term and preterm labor. Cervical biopsies were taken from 59 women: 21 at preterm labor, 24 at term labor, 10 at term not in labor and 4 from non-pregnant women. mRNA was analyzed with real-time RT-PCR and protein expression and/or secretion with immunohistochemistry and ELISA. There was an upregulation of mRNA for IL-10, IL-13, IL-1 alpha and IL-1 beta in the laboring groups, while mRNA for IL-12 and IL-18 was downregulated. IL-4 mRNA was detected more frequently, while IL-12 mRNA expression was lower, in the preterm labor group than in the term labor group. The protein levels of IL-4 and IL-12 were lower and IL-18 tended to be higher in the labor groups, while IL-10 protein levels were unaffected by labor. IL-4 protein levels were significantly higher in the preterm subgroup with bacterial infection than in the non-infected group. IL-10 had higher expression in squamous epithelium at preterm labor than at term. In conclusion, the major changes in pro-inflammatory and anti-inflammatory cytokine mRNA and protein expression in cervix occur during the labor process irrespective of the length of gestation. Our results indicate that dysregulation of anti-inflammatory cytokines in the human cervix could be involved in the pathogenesis of preterm labor.

  • 47.
    Dölfors, Fredrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för biologisk grundutbildning.
    Växters effektorutlösta försvars funktionoch evolution: Ett uthålligt skydd mot patogener?2014Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
    Abstract [sv]

    Diversiteten bland gener som ger resistens (R) mot infektionssjukdomar är mycket stor i växtriket, särskilt i den effektorutlösta klassen av försvaret. Denna artikel beskriver interaktioner mellan växters effektorutlösta fösvar och patogeners effektorproteiner och undersöker evolutionära och genetiska mekanismer för uppkomsten av ny resistens. R-genprodukter har en typisk domänstruktur och interagerar både direkt och indirekt med patogeners effektorproteiner.Vid kontakt med ett effektorprotein utlöses en försvarsrespons som kan förhindra fortsatt patogen tillväxt. Flera genetiska mekanismer verkar samtidigt på R-gener, något som resulterar i en hög hastighet för uppkomst av nya R-varianter. Den intima samevolution som existerar hos många patogen-växtsystem formar det evolutionära utvecklingsmönstret av R-gener. Diversifierande positiv selektion via den biologiska kapprustningsmodellen och bevarande negativ frekvensberoende selektion är båda viktiga samevolutionära processer. Denna artikel indikerar att växters immunförsvar är anpassningsbart och robust, men belyser också den kunskapsbrist som råder inom resistensforskningen.

  • 48.
    Eberhardson, Michael
    et al.
    Karolinska Inst, Dept Med, Ctr Bioelect Med, Bioclinicum, Solna, Sweden;Karolinska Univ Hosp, Solna, Sweden.
    Hedin, Charlotte R. H.
    Karolinska Univ Hosp, Solna, Sweden;Karolinska Inst, Dept Med Solna, Solna, Sweden.
    Carlson, Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Tarnawski, Laura
    Karolinska Inst, Dept Med, Ctr Bioelect Med, Bioclinicum, Solna, Sweden;Karolinska Univ Hosp, Solna, Sweden.
    Levine, Yaakov A.
    SetPoint Med, Valencia, CA USA.
    Olofsson, Peder S.
    Karolinska Inst, Dept Med, Ctr Bioelect Med, Bioclinicum, Solna, Sweden;Karolinska Univ Hosp, Solna, Sweden.
    Towards improved control of inflammatory bowel disease2019Ingår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 89, nr 3, artikel-id e12745Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Inflammatory bowel disease (IBD) is characterized by activation of both the innate and adaptive immune system in genetically susceptible individuals, resulting in chronic intestinal inflammation. The triggers that initiate and perpetuate this continuous inflammation are the subject of much speculation and research, although the central role of the intestinal microbiota is recognized, and is even a target for treatment in some circumstances. The mainstay of modern IBD treatment is suppression of the immune response towards as yet unspecified antigens, and conventional therapy includes corticosteroids, 5-aminosalicylic acid (5-ASA), thiopurines and methotrexate. Reducing activity of specific mediators has proven efficacious, including adhesion molecules, such as the gut-homing integrin alpha(4)beta(7) expressed on the surface of circulating immune cells, and cytokines, such as tumour necrosis factor alpha (TNF-alpha). This has been achieved using biologic agents including monoclonal antibodies. Recent discoveries in immunology and neuroscience have revealed that signals in the peripheral nervous system regulate inflammation, including levels of TNF-alpha. The understanding of the mechanisms of the neuro-immune communication involved in inflammation control in the gut is evolving, but is as yet incomplete. Clinical studies using implanted vagus nerve stimulators for treatment of IBD show encouraging results. Accordingly, the neural reflex control of inflammation is emerging as a potential therapeutic target in treatment of IBD. Here, we review current therapeutic options and neural reflex control of gut immunity in the context of intestinal inflammation.

  • 49. Ek, Weronica
    et al.
    Sahlqvist, Anna-Stina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Autoimmunitet.
    Crooks, Lucy
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Sgonc, Roswitha
    Dietrich, Hermann
    Wick, Georg
    Ekwall, Olov
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Autoimmunitet.
    Andersson, Leif
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Carlborg, Örjan
    Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Kämpe, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Autoimmunitet.
    Kerje, Susanne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Mapping QTL affecting a systemic sclerosis-like disorder in a cross between UCD-200 and red jungle fowl chickens2012Ingår i: Developmental and Comparative Immunology, ISSN 0145-305X, E-ISSN 1879-0089, Vol. 38, nr 2, s. 352-359Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Systemic sclerosis (SSc) or scleroderma is a rare, autoimmune, multi-factorial disease characterized by early microvascular alterations, inflammation, and fibrosis. Chickens from the UCD-200 line develop a hereditary SSc-like disease, showing all the hallmarks of the human disorder, which makes this line a promising model to study genetic factors underlying the disease. A backcross was generated between UCD-200 chickens and its wild ancestor - the red jungle fowl and a genome-scan was performed to identify loci affecting early (21days of age) and late (175days of age) ischemic lesions of the comb. A significant difference in frequency of disease was observed between sexes in the BC population, where the homogametic males were more affected than females, and there was evidence for a protective W chromosome effect. Three suggestive disease predisposing loci were mapped to chromosomes 2, 12 and 14. Three orthologues of genes implicated in human SSc are located in the QTL region on chromosome 2, TGFRB1, EXOC2-IRF4 and COL1A2, as well as CCR8, which is more generally related to immune function. IGFBP3 is also located within the QTL on chromosome 2 and earlier studies have showed increased IGFBP3 serum levels in SSc patients. To our knowledge, this study is the first to reveal a potential genetic association between IGFBP3 and SSc. Another gene with an immunological function, SOCS1, is located in the QTL region on chromosome 14. These results illustrate the usefulness of the UCD-200 chicken as a model of human SSc and motivate further in-depth functional studies of the implicated candidate genes.

  • 50.
    Eliasson, Hanna
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Development of immunological methods and Real-Time PCR for detection of Macadamia nut (Macadamia spp.)2005Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats
    Abstract [en]

    A new European labeling directive (2003/89/EC) states that certain foods and products derived thereof must always be declared. Among the tree nuts specified is Macadamia nut (Macadamia spp.). During the last few years, cases of IgE-allergic reactions, even severe anaphylaxes, have been reported. Reliable methods for the detection of this nut are needed.

    Protein from Macadamia nuts was isolated. Polyacrylamide gel electrophoresis in SDS revealed two main protein bands of about 20 and 50kDa. These protein bands were cut and extracted from the gel and rabbits were immunized with each protein.

    Immunoblotting showed dominant reactivity with the respective antigens. The antisera were further tested for specificity in immunodiffusion and in rocket immunoelectrophoresis.

    In addition, a specific DNA-method was developed, based on Real-Time PCR using Macadamia vicilin as target sequence. Two different primer pairs were tested. Specificity was tested against potentially related nuts. Optimisation of primer and probe concentrations was performed. The limit of detection was 2-4 pg DNA, corresponding to a macadamia nut concentration of 50 to 100 μg per g. In a background of soybean DNA, down to 0,01 % macadamia DNA could be detected.

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