uu.seUppsala University Publications
Change search
Refine search result
1 - 29 of 29
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1. Ahrens, Richard
    et al.
    Waddell, Amanda
    Seidu, Luqman
    Blanchard, Carine
    Carey, Rebecca
    Forbes, Elizabeth
    Lampinen, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wilson, Tara
    Cohen, Elizabeth
    Stringer, Keith
    Ballard, Edgar
    Munitz, Ariel
    Xu, Huan
    Lee, Nancy
    Lee, James J.
    Rothenberg, Marc E.
    Denson, Lee
    Hogan, Simon P.
    Intestinal Macrophage/Epithelial Cell-Derived CCL11/Eotaxin-1 Mediates Eosinophil Recruitment and Function in Pediatric Ulcerative Colitis2008In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 181, no 10, p. 7390-7399Article in journal (Refereed)
    Abstract [en]

    Clinical studies have demonstrated a link between the eosinophil-selective chemokines, eotaxins (eotaxin-1/CCL11 and eotaxin-2/CCL24), eosinophils, and the inflammatory bowel diseases, Crohn's disease and ulcerative colitis (UC). However, the cellular source and individual contribution of the eotaxins to colonic eosinophilic accumulation in inflammatory bowel diseases remain unclear. In this study we demonstrate, by gene array and quantitative PCR, elevated levels of eotaxin-1 mRNA in the rectosigmoid colon of pediatric UC patients. We show that elevated levels of eotaxin-1 mRNA positively correlated with rectosigmoid eosinophil numbers. Further, colonic eosinophils appeared to be degranulating, and the levels positively correlated with disease severity. Using the dextran sodium sulfate (DSS)-induced intestinal epithelial injury model, we show that DSS treatment of mice strongly induced colonic eotaxin-1 and eotaxin-2 expression and eosinophil levels. Analysis of eosinophil-deficient mice defined an effector role for eosinophils in disease pathology. DSS treatment of eotaxin-2(-/-) and eotaxin-1/2(-/-) mice demonstrated that eosinophil recruitment was dependent on eotaxin-1. In situ and immunofluorescence analysis-identified eotaxin-1 expression was restricted to intestinal F4/80(+)CD11b(+) macrophages in DSS-induced epithelia] injury and to CD68(+) intestinal macrophages and the basolateral compartment of intestinal epithelial cells in pediatric UC. These data demonstrate that intestinal macrophage and epithelial cell-derived eotaxin-1 plays a critical role in the regulation of eosinophil recruitment in colonic eosinophilic disease such as pediatric UC and provides a basis for targeting the eosinophil/eotaxin-1 axis in UC.

  • 2.
    Amcoff, K.
    et al.
    Orebro Univ, Dept Gastroenterol, Fac Med & Hlth, Orebro, Sweden..
    Cao, Y.
    Univ Orebro, Sch Med Sci, Clin Epidemiol & Biostat, Orebro, Sweden..
    Zhulina, Y.
    Orebro Univ, Dept Gastroenterol, Fac Med & Hlth, Orebro, Sweden..
    Lampinen, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Halfvarson, J.
    Orebro Univ, Dept Gastroenterol, Fac Med & Hlth, Orebro, Sweden..
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Prognostic significance of eosinophil granule proteins in inflammatory bowel disease2018In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, p. S181-S182Article in journal (Other academic)
  • 3.
    Amcoff, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology. Orebro Univ, Fac Med & Hlth, Dept Gastroenterol, Orebro, Sweden.
    Cao, Yang
    Orebro Univ, Sch Med Sci, Clin Epidemiol & Biostat, Orebro, Sweden;Karolinska Inst, Inst Environm Med, Unit Biostat, Stockholm, Sweden.
    Zhulina, Yaroslava
    Orebro Univ, Fac Med & Hlth, Dept Gastroenterol, Orebro, Sweden.
    Lampinen, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Halfvarson, Jonas
    Orebro Univ, Fac Med & Hlth, Dept Gastroenterol, Orebro, Sweden.
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Prognostic significance of faecal eosinophil granule proteins in inflammatory bowel disease2019In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 54, no 10, p. 1237-1244Article in journal (Refereed)
    Abstract [en]

    Background: Non-invasive markers for predicting relapse would be a useful tool for the management of patients with inflammatory bowel disease. Eosinophil granulocytes and their granule proteins eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) have previously been shown to reflect disease activity in Crohn's disease and ulcerative colitis.

    Aim: To examine the capacity of faecal ECP and EDN to predict relapse in ulcerative colitis and Crohn's disease, and to compare these proteins with faecal calprotectin.

    Methods: Patients with Crohn's disease (n?=?49) and ulcerative colitis (n?=?55) were followed prospectively until relapse or end of the two-year study period. Faecal samples were obtained every third month. The predictive value of ECP and EDN was assessed in Cox regression models.

    Results: In ulcerative colitis, a doubled EDN or ECP concentration was associated with a 31% and 27% increased risk of relapse, respectively. EDN levels were increased both at relapse and three months prior. By contrast, in Crohn's disease, the concentration of EDN was higher among patients in remission than in those who relapsed. Correlations between faecal calprotectin, ECP and EDN were observed in both diseases.

    Conclusions: We demonstrate that the risk of relapse in ulcerative colitis can be predicted by consecutively measuring faecal EDN every third month, and suggest EDN as a complementary faecal marker to calprotectin to predict future relapse in ulcerative colitis. Our finding of higher EDN in Crohn's disease-patients staying in remission than in those who relapsed indicates different functions of the protein in ulcerative colitis and Crohn's disease.

  • 4.
    Amcoff, Karin
    et al.
    Univ Orebro, Fac Med & Hlth, Dept Gastroenterol, SE-70182 Orebro, Sweden..
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Lampinen, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Magnuson, Anders
    Univ Orebro, Sch Med Sci, Clin Epidemiol & Biostat, Orebro, Sweden..
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Halfvarson, Jonas
    Univ Orebro, Fac Med & Hlth, Dept Gastroenterol, SE-70182 Orebro, Sweden..
    Clinical implications of assay specific differences in f-calprotectin when monitoring inflammatory bowel disease activity over time2017In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 3, p. 344-350Article in journal (Refereed)
    Abstract [en]

    Objective: With several faecal calprotectin (FC) assays on the market, it has been difficult to define a uniform threshold for discriminating between remission and active disease in patients with inflammatory bowel disease (IBD). We aimed to compare the results of different FC-assays in IBD patients, followed over time.Material and methods: IBD patients provided faecal samples and reported clinical activity every third month prospectively over a two year period. FC was measured with two ELISA - (Buhlmann and Immunodiagnostik) and one automated fluoroimmunoassay (Phadia).Results: In total, 13 patients provided 91 faecal samples. The median (IQR) concentration of FC was higher at active disease than at remission for all assays: Buhlmann 845 (1061-226) g/g versus 62 (224-39) g/g, Phadia 369 (975-122) g/g versus 11 (52-11) g/g, and Immundiagnostik 135 (302-69) g/g versus 8 (56-4) g/g. The Buhlmann assay produced the largest absolute difference but the corresponding relative difference seemed to be more pronounced when analysed by the Phadia - (ratio of means 8.5; 95% CI 3.3-21.9) or the Immundiagnostik assay (ratio of means 7.4; 95% CI 3.1-17.6) than by the Buhlmann assay (ratio of means 5.3; 95% CI 2.7-10.6). Consequently, the specificity for discriminating active disease from remission varied between assays (34-75%) when the cut-off 50g/g was used, whereas the differences in sensitivity were less pronounced.Conclusions: Cross-comparisons revealed overall poor agreement between the assays as well as differences in the dynamics of FC. These findings suggest that standardisation of the method is needed to implement FC as a disease monitoring tool at large-scale.

  • 5. Carlson, Marie
    et al.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lampinen, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    C3b-induced eosinophil degranulation involves PI3-kinases and is inhibited by protein kinase C activity2011In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 119, no 2, p. 119-126Article in journal (Refereed)
    Abstract [en]

    Selective release of individual eosinophil granule proteins has been demonstrated in eosinophilic conditions and in vitro using different stimuli. The aim of this study was to investigate if selective release of eosinophil cationic protein (ECP), eosinophil protein X/eosinophil derived-neurotoxin (EPX/EDN) and eosinophil peroxidase (EPO) could be due to the involvement of different signal transduction pathways. Peripheral blood granulocytes from healthy donors were incubated with Wortmannin, LY294002, Genistein, Staurosporine, GÖ6976 or PD98059 prior to the induction of degranulation by C3b. The released amounts of ECP, EPO and EPX/EDN were determined by immunoassays, and related to the total cell content of respective protein. Wortmannin caused a significant, dose-dependent inhibition of all three granule proteins. LY294002 (10(-6)  M) also inhibited the release of all proteins. Genistein (10(-6)  M) inhibited the release of ECP, whereas the release of EPO was increased. However, there was a tendency towards similar concentration-dependent patterns of release of all three proteins. Staurosporine (10(-7)  M), GÖ6976 (10(-6)  M) and PD98059 (10(-5)  M) caused an increased release of the three proteins. PI3-kinases play an important role in the C3b-induced release of ECP, EPO and EPX/EDN, whereas protein kinase C seems to have inhibitory effects on C3b-induced degranulation.

  • 6.
    Hagforsen, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Lampinen, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Paivandy, Aida
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Weström, Simone
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Velin, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Öberg, S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Pejler, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Rollman, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Siramesine causes preferential apoptosis of mast cells in skin biopsies from psoriatic lesions2017In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 177, no 1, p. 179-187Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Skin mast cells are implicated as detrimental effector cells in various inflammatory skin diseases such as contact eczema, atopic dermatitis and psoriasis. Selective reduction of cutaneous mast cells, e.g. by inducing targeted apoptosis, might prove a rational and efficient therapeutic strategy in dermatoses negatively influenced by mast cells.

    OBJECTIVES: The objective of the present study was to evaluate whether a lysosomotropic agent such as siramesine can cause apoptosis of mast cells present in psoriatic lesions.

    MATERIALS AND METHODS: Punch biopsies were obtained from lesional and uninvolved skin in 25 patients with chronic plaque psoriasis. After incubation with siramesine, the number of tryptase-positive mast cells and their expression of interleukin (IL)-6 and IL-17 was analysed. Skin biopsies were digested to allow flow cytometric analysis of the drug's effect on cutaneous fibroblasts and keratinocytes.

    RESULTS: Siramesine caused a profound reduction in the total number of mast cells in both lesional and uninvolved psoriatic skin biopsies without affecting the gross morphology of the tissue. The drug reduced the density of IL-6- and IL-17-positive mast cells, and showed antiproliferative effects on epidermal keratinocytes but had no apparent cytotoxic effect on keratinocytes or dermal fibroblasts.

    CONCLUSIONS: Considering the pathophysiology of psoriasis, the effects of siramesine on cutaneous mast cells may prove favourable from the therapeutic aspect. The results encourage further studies to assess the usefulness of siramesine and other lysosomotropic agents in the treatment of cutaneous mastocytoses and inflammatory skin diseases aggravated by dermal mast cells.

  • 7.
    Hagforsen, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Paivandy, Aida
    Lampinen, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Weström, Simone
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Calounova, Gabriela
    Melo, Fabio R.
    Rollman, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Pejler, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Ablation of human skin mast cells in situ by lysosomotropic agents2015In: Experimental dermatology, ISSN 0906-6705, E-ISSN 1600-0625, Vol. 24, no 7, p. 516-521Article in journal (Refereed)
    Abstract [en]

    Mast cells are known to have a detrimental impact on numerous types of inflammatory skin diseases such as contact dermatitis, atopic eczema and cutaneous mastocytosis. Regimens that dampen skin mast cell-mediated activities can thus offer an attractive therapeutic option under such circumstances. As mast cells are known to secrete a large array of potentially pathogenic compounds, both from preformed stores in secretory lysosomes (granules) and after de novo synthesis, mere inhibition of degranulation or interference with individual mast cell mediators may not be sufficient to provide an effective blockade of harmful mast cell activities. An alternative strategy may therefore be to locally reduce skin mast cell numbers. Here, we explored the possibility of using lysosomotropic agents for this purpose, appreciating the fact that mast cell granules contain bioactive compounds prone to trigger apoptosis if released into the cytosolic compartment. Based on this principle, we show that incubation of human skin punch biopsies with the lysosomotropic agents siramesine or Leu-Leu methyl ester preferably ablated the mast cell population, without causing any gross adverse effects on the skin morphology. Subsequent analysis revealed that mast cells treated with lysosomotropic agents predominantly underwent apoptotic rather than necrotic cell death. In summary, this study raises the possibility of using lysosomotropic agents as a novel approach to targeting deleterious mast cell populations in cutaneous mastocytosis and other skin disorders negatively influenced by mast cells.

  • 8. Karlsson, Mats
    et al.
    Linton, Ludvig
    Lampinen, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Karlen, Per
    Glise, Hans
    Befrits, Ragnar
    Janczewska, Izabella
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Winqvist, Ola
    Eberhardson, Michael
    Naive T cells correlate with mucosal healing in patients with inflammatory bowel disease2014In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 49, no 1, p. 66-74Article in journal (Refereed)
    Abstract [en]

    Background. In previous studies, adaptive immune responses involving T-helper cells have been shown to play an important role in inflammatory bowel diseases (IBDs). Methods. The aim of this study was to investigate any correlation between the degree of mucosal inflammation and the phenotype of gut-infiltrating T-helper cells. Biopsies from intestinal mucosa were obtained and intestinal T cells were analyzed with regard to activity and maturation markers. Patients with active colitis (39 with Crohn's disease and 47 with ulcerative colitis) were included and treated with corticosteroids, biologicals or leukocytapheresis. Flow cytometry was used to analyze activation marker expression on gut-infiltrating T-helper cells. Results. Mucosal healing was reflected by almost 100% increase of CD62L expression in mucosal T cells in patients in remission compared to those with active inflammation (p < 0.01). The frequency of mucosal-naive CD4(+)CD45RA(+)T cells was reduced by 50% in mucosa displaying remission (5.3% compared to 12% of the total amount and CD4(+) T cells, p < 0.001). Surprisingly, the proportion of early activated T-helper cells (CD4(+)CD69(+)) did not differ between mucosa in remission and non-remission (43% and 42%, respectively). Moreover, no change in memory T-helper cells (CD4(+)CD45RO(+)) was observed (64% compared to 66%). The findings were independent of diagnosis (Crohn's disease or ulcerative colitis) or mode of treatment. Conclusion. This study suggests that a reduced recruitment of naive T-helper cells and increased frequency of T-helper cells with lymph node homing marker expression reflect mucosal healing in IBD. Surprisingly, the degree of activation of mucosal T-helper cells did not correlate with disease remission.

  • 9. Karlsson, Mats
    et al.
    Linton, Ludvig
    Lampinen, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Karlen, Per
    Glise, Hans
    Befrits, Ragnar
    Janczewska, Izabella
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Winqvist, Ola
    Eberhardson, Michael
    Naive T cells in the gut: how to really find them?2014In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 49, no 4, p. 518-518Article in journal (Refereed)
  • 10.
    Kämpe, Mary
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Lampinen, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stolt, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Stålenheim, Gunnemar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    PI3-Kinase Regulates Eosinophil and Neutrophil Degranulation in Patients with Allergic Rhinitis and Allergic Asthma Irrespective of Allergen Challenge Model2012In: Inflammation, ISSN 0360-3997, E-ISSN 1573-2576, Vol. 35, no 1, p. 230-239Article in journal (Refereed)
    Abstract [en]

    The PI3K pathway plays a major role in many vital cell processes. Our primary aim was to investigate signalling through PI3K for in vitro degranulation from allergen-primed eosinophils and neutrophils in allergic rhinitis and allergic asthma after seasonal and experimental allergen challenge. Nine patients with allergic rhinitis, eight with allergic asthma and four controls were studied during birch pollen season and after nasal and bronchial allergen challenge. Primed blood eosinophils and neutrophils were stimulated for in vitro degranulation with C3b-coated Sephadex particles, after prior incubation with Wortmannin, a PI3K inhibitor. The released amounts of eosinophil cationic protein (ECP), eosinophil peroxidase (EPO) and myeloperoxidase (MPO) were measured by radioimmunoassay. Wortmannin (10(-6) to 10(-9) M) inhibited ECP, EPO and MPO release in a dose-dependent manner in allergic rhinitis and allergic asthma in all three allergen challenge models. Inhibition of ECP release tended to be lower in the asthmatics in all allergen challenge models, statistically significant compared to the controls during season for 10(-8) M Wortmannin (p = 0.01). A clear propensity towards less inhibition in the rhinitic patients was seen after nasal and bronchial challenge compared to seasonal exposure, significant for ECP (10(-8) M Wortmannin; p = 0.034 and 0.002, respectively). Signalling through PI3K is clearly involved in ECP, EPO and MPO release in allergic rhinitis and allergic asthma irrespective of allergen challenge model. Allergic asthma demonstrated less inhibition of ECP release via PI3K during pollen season, indicating that other pathways play a greater role in eosinophil degranulation in allergic asthma than allergic rhinitis.

  • 11. Lampinen, M
    et al.
    Carlson, M
    Sangfelt, P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. gastroenterologi.
    Taha, Y
    Thörn, M
    Lööf, L
    Raab, Y
    Venge, P
    IL-5 and TNF-alpha participate in recruitment of eosinophils to intestinal mucosa in ulcerative colitis.2001In: Dig Dis Sci, ISSN 0163-2116, Vol. 46, no 9, p. 2004-9Article in journal (Other academic)
  • 12.
    Lampinen, M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Rak, S
    Venge, P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    The role of interleukin-5, interleukin-8 and RANTES in the chemotactic attraction of eosinophils to the allergic lung (see comments)1999In: Clin Exp Allergy, Vol. 29, p. 314-Article in journal (Refereed)
  • 13.
    Lampinen, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Backman, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Winqvist, Ola
    Rorsman, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Rönnblom, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sangfelt, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Different regulation of eosinophil activity in Crohn's disease compared with ulcerative colitis2008In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 84, no 6, p. 1392-1399Article in journal (Refereed)
    Abstract [en]

    The aim of this investigation was to study the involvement of eosinophil and neutrophil granulocytes in different stages of Crohn's disease (CD) and ulcerative colitis (UC). Biopsy samples were taken from the right flexure of the colon and from the rectum in patients with active (n=12) and inactive colonic CD (n=7), patients with active (n=33) and inactive UC (n=24), and from control subjects (n=11). Cell suspensions from biopsies and blood were analyzed by flow cytometry with regards to activation markers and viability. Immunohistochemistry was used to evaluate cell number and degranulation. Blood eosinophils were cultured with Th1 and Th2 cytokines, and the expression of activity markers was assessed by flow cytometry. Eosinophil number, viability, and activity were increased during active CD and UC compared with controls. The activity, assessed as CD44 expression, tended to diminish during inactive CD but was increased further in quiescent UC. Neutrophil number and activity were increased only during inflammation in both diseases. Culture of blood eosinophils with IL-5 and IL-13 caused increased CD44 expression, whereas IL-5 and IFN-gamma induced elevated CD69 expression. We observed different patterns of eosinophil activation in CD and UC, with the highest CD44 expression during quiescent UC. Our in vitro experiments with recombinant cytokines suggest that the diverse mechanisms of eosinophil activation in CD and UC are a result of different cytokine milieus (Th1 vs. Th2). In contrast, neutrophil activation reflects the disease activity in CD and UC, irrespective of Th cell skewing.

  • 14.
    Lampinen, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Douhan-Håkansson, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Cytokine-regulated accumulation of eosinophils in inflammatory disease2004In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 59, no 8, p. 793-805Article in journal (Refereed)
    Abstract [en]

    The role of cytokines in the accumulation of eosinophil granulocytes in inflamed tissue has been studied extensively during recent years, and these molecules have been found to participate throughout the whole process of eosinophil recruitment. Haematopoietic cytokines such as IL-3, IL-5 and GM-CSF stimulate the proliferation and differentiation of eosinophils in the bone marrow, and the release of mature eosinophils from the bone marrow into the blood is probably promoted by IL-5. Priming of eosinophils in the blood following, for example, allergen challenge is performed mainly by IL-3, IL-5 and GM-CSF. An important step in the extravasation of eosinophils is their adhesion to the vascular endothelium. Adhesion molecules are upregulated by, e.g. IL-1, IL-4, TNF-alpha and IFN-gamma and the same cytokines may also increase the affinity of adhesion molecules both on eosinophils and endothelial cells. Finally, a number of cytokines have been shown to act as eosinophil chemotactic factors, attracting the cells to the inflammatory focus in the tissue. Some of the most important eosinophil chemoattractant cytokines are IL-5, IL-8, RANTES, eotaxin, eotaxin-2, eotaxin-3, MCP-3, MCP-4 and TNF-alpha. Th2 cells, mast cells and epithelial cells are important sources of proinflammatory cytokines, but in recent years, the eosinophils have also been recognized as cytokine-producing and thereby immunoregulatory cells. The aim of this paper is to review the role of cytokines in the process of eosinophil recruitment in asthma, allergy and ulcerative colitis.

  • 15.
    Lampinen, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Fredricsson, Annika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Vessby, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Martinez, Johana Fernandez
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Wanders, Alkwin
    Umeå Univ, Dept Med Biosci, Umeå, Sweden.
    Rorsman, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Downregulated eosinophil activity in ulcerative colitis with concomitant primary sclerosing cholangitis2018In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 104, no 1, p. 173-183Article in journal (Refereed)
    Abstract [en]

    Primary sclerosing cholangitis (PSC) is a chronic bile duct inflammation strongly connected to ulcerative colitis (UC). PSC is associated with an increased risk of colon cancer, but the link between the intestinal and the bile duct inflammation is still unknown. Also, the involvement of intestinal immune cells in the pathogenesis of PSC remains to be determined. The eosinophil granulocyte is one of the immune cells implicated in the inflammatory process of ulcerative colitis. This study was performed to determine how the accumulation and activation of intestinal eosinophils may differ between UC with and without concomitant PSC, and how this may be influenced by the cytokine/chemokine profile of the intestinal compartment. Eosinophils from peripheral blood and multiple parts of the colon were analyzed by flow cytometry. The intestinal level of inflammatory mediators was assessed using a multiplex proximity extension assay and a quantitative immunoassay. We found that colonic eosinophils were more abundant in both UC and PSC-UC compared with controls, but that their expression of activation markers was significantly increased in UC only. The colonic level of pro-inflammatory cytokines was increased in active UC but not in PSC-UC. In conclusion, we show for the first time that eosinophil activation phenotype discriminates between UC and PSC-UC, and that this may depend on the local cytokine profile of the colonic mucosa. Lower expression of activation markers on eosinophils in UC with concomitant PSC may depend on the local protein profile of the colonic mucosa.

  • 16.
    Lampinen, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Fredricsson, Annika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Vessby, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Wanders, A.
    Umea Univ, Med Biosci, Umea, Sweden..
    Rorsman, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology. Uppsala Univ, Med Sci, Uppsala, Sweden..
    Expression of the liver homing receptor CXCR3+on colonic CD8+T lymphocytes in patients with primary sclerosing cholangitis provides a possible link between colonic and biliary duct inflammation2016In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 10, p. S109-S109Article in journal (Other academic)
  • 17.
    Lampinen, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hakansson, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Interleukin-2 inhibits eosinophil migration but is counteracted by IL-52001In: Clin Exp Allergy, Vol. 31, p. 249-Article in journal (Refereed)
  • 18. Lampinen, Maria
    et al.
    Håkansson, Lena Douhan
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Klinisk kemi.
    Venge, Per
    Klinisk kemi.
    Albumin stimulation of eosinophil migration involves PI3-kinases and is associated with diminished eosinophil CD49d and CD49f expression.2006In: Int Arch Allergy Immunol, ISSN 1018-2438, Vol. 140, no 2, p. 113-20Article in journal (Refereed)
  • 19.
    Lampinen, Maria
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Medicin.
    Rönnblom, Anders
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. OTM.
    Amin, Kawa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. klinisk kemi.
    Kristjansson, Gudjon
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. OTM.
    Rorsman, Fredrik
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. OTM.
    Sangfelt, Per
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. OTM.
    Säfsten, Bengt
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. OTM.
    Wagner, Michael
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. OTM.
    Wanders, Alkwin
    Department of Genetics and Pathology. patologi.
    Winqvist, Ola
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Medicin.
    Carlson, Marie
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. OTM.
    Eosinophil granulocytes are activated during the remission phase of ulcerative colitis.2005In: Gut, ISSN 0017-5749Article in journal (Refereed)
  • 20.
    Lampinen, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Vessby, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Fredricsson, Annika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Wanders, Alkwin
    Rorsman, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    High serum sCD40 and a distinct colonic T cell profile in ulcerative colitis associated with primary sclerosing cholangitis.2019In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 13, no 3, p. 341-350Article in journal (Refereed)
    Abstract [en]

    Background and aims: There is a strong association between primary sclerosing cholangitis (PSC) and ulcerative colitis (UC), but the immunological link between the two diseases is obscure. We compared serum cytokine profiles of patients with PSC-UC and UC, and investigated a number of selected cytokines in colonic biopsy samples. We also assessed the presence and activation of T-cells in peripheral blood and colonic mucosa.

    Methods: Serum samples from 22 patients with PSC-UC, 28 patients with UC and 19 controls were analyzed by a proximity extension assay including 92 inflammatory cytokines. Biopsies from caecum, sigmoid colon and rectum were collected from the same patients. Quantitative analysis for IFN-γ, IL-2, IL-4, IL-5, IL-13, IL-17A/ E/F, IL-21, IL-22, IL-23 and IL-27 was carried out on tissue homogenates. T-cell phenotype was evaluated by flow cytometry.

    Results: By multivariate analysis we identified a cluster of serum cytokines with higher levels in PSC-UC, and sCD40 in particular was strongly associated to this patient group. In contrast, colonic cytokines were only modestly increased in PSC-UC, whereas several Th1, Th2 and Th17-associated cytokines were increased in UC. Patients with PSC-UC had increased colonic levels of CXCR3-positive CD8+ T-cells but fewer CD25-positive CD4+ T-cells. An increased CRTH2/CXCR3-quote indicated a predominance of Th-2 type CD4+ T-cells in UC-patients.

    Conclusions: Our study reveals different cytokine- and T-cell profiles in PSC-UC and UC, with higher systemic levels of cytokines in PSC-UC, and a more pronounced colonic inflammation in UC. Serum sCD40 could potentially be investigated as a marker for PSC in UC.

  • 21.
    Lampinen, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Waddell, Amanda
    Ahrens, Richard
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Hogan, Simon P.
    CD14(+)CD33(+) myeloid cell-CCL11-eosinophil signature in ulcerative colitis2013In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 94, no 5, p. 1061-1070Article in journal (Refereed)
    Abstract [en]

    This study tested the hypothesis that eotaxins (CCL11, CCL24, and CCL26) and IL-5 contribute to eosinophil recruitment to the intestine in UC and that intestinal macrophages are important producers of CCL11 in this disease. Peripheral blood and rectal biopsy samples were obtained from patients with active (n=18) and quiescent UC (n=9), and control patients (n=7). Eosinophil and macrophage levels and activation were analyzed by flow cytometry. Rectal mRNA levels of CCL11, CCL24, CCL26, and IL-5 were determined by qRT-PCR. The cellular source of CCL11 was visualized by immunofluorescence analyses. Eosinophil numbers were elevated in the blood and rectum of active and quiescent UC patients compared with controls. Levels of activated eosinophils (CD66b(high)) correlated with disease severity. Rectal CCL11, CCL24, and CCL26 mRNA levels were increased in active UC, whereas only CCL11 was elevated in quiescent UC. Levels of CCL11, but not CCL24 and CCL26, positively correlated with eosinophil numbers. Numbers of CD14(+)CD33(+) cells correlated with CCL11 and eosinophil levels. Immunofluorescence analyses revealed the presence of CD14(+)CCL11(+) mononuclear cells in colonic biopsies in UC. These results support the hypothesis that CCL11 contributes to eosinophil recruitment in UC and that intestinal myeloid cells are a source of CCL11. Interestingly, rectal levels of CCL24, CCL26, and IL-5 only increase during active UC, coinciding with further elevation of eosinophil numbers and with the activation of rectal eosinophils. In conclusion, there is a link among CD14(+)CD33(+) myeloid cells, CCL11, and eosinophils in adult UC.

  • 22.
    Lampinen, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Öberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Selective priming of peripheral blood eosinophils in patients with idiopathic hypereosinophilic syndrome2006In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 114, no 11, p. 757-763Article in journal (Refereed)
    Abstract [en]

    The idiopathic hypereosinophilic syndrome (HES) is characterised by blood eosinophilia associated with organ involvement. Elevated numbers of blood neutrophils have been observed during episodes of active HES. However, an increased responsiveness of eosinophils to chemotactic and chemokinetic stimuli may explain the selective eosinophil infiltration of the tissue. We have studied the migratory responses of blood eosinophils and neutrophils from 9 patients with HES and from 13 healthy control subjects. Chemokinetic and chemotactic responses to factors acting on both cell types were analysed by means of a modification of the Boyden chamber technique. We found increased migratory responses of the eosinophils, but not of the neutrophils, from the patients with HES. Increased blood neutrophil counts in three of the patients did not coincide with alterations of the neutrophil migratory responses. Our finding of increased migratory responses of eosinophils from patients with HES towards non-specific chemoattractants suggests selective priming of eosinophils in this disease. Interleukin (IL)-5 has previously been shown to prime eosinophils for migratory responses, and successful anti-IL-5 therapy of patients with HES indicates an important role for this cytokine in the development of hypereosinophilia.

  • 23.
    Mary, Kämpe
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Stolt, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Lampinen, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Stålenheim, Gunnemar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Patients with allergic rhinitis and allergic asthma share the same pattern of eosinophil and neutrophil degranulation after allergen challenge2011In: Clinical and Molecular Allergy, ISSN 1476-7961, E-ISSN 1476-7961, Vol. 9, no 1, p. 3-Article in journal (Refereed)
    Abstract [en]

    Background:

    Patients with allergic rhinitis and allergic asthma demonstrate comparable local and systemic eosinophil inflammation, and yet they present with different clinical pictures. Less is even known about the contribution of neutrophil inflammation in allergic diseases. The aim of the study was to examine the propensity and selectivity of granule release from primed systemic eosinophils and neutrophils in allergic rhinitis and allergic asthma after seasonal and experimental allergen exposure. We hypothesize that the dissimilar clinical manifestations are due to diverse eosinophil and neutrophil degranulation. 

    Methods: 

    Nine birch pollen allergic patients with rhinitis, eight with asthma and four controls were studied during pollen season and after nasal and bronchial allergen challenge. Eosinophils and neutrophils were incubated in vitro with assay buffer and opsonized Sephadex particles for spontaneous and C3b-induced granule protein release. The released amount of eosinophil cationic protein (ECP), eosinophil peroxidase (EPO) and myeloperoxidase (MPO) was measured by specific radioimmunoassay.

    Results:

    C3b-induced degranulation resulted in increased release of ECP and MPO from primed blood eosinophils and neutrophils in both allergic rhinitis and allergic asthma during pollen season and after both nasal and bronchial challenge (p-values 0.008 to 0.043). After bronchial challenge, the ECP release was significantly higher in the rhinitic group compared to the asthmatic group [19.8 vs. 13.2 %, (p=0.010)]. The propensity for EPO release was weak in all challenge models but followed the same pattern in both allergic groups.

    Conclusion:  

    Systemically allergen primed eosinophils and neutrophils have similar patterns of degranulation after allergen exposure in allergic rhinitis and allergic asthma. The released amount of ECP, EPO and MPO was similar in all allergen challenge models in both allergic groups. Our results indicate that other mechanisms than the magnitude of eosinophil and neutrophil inflammation or the degranulation pattern of the inflammatory cells determines whether or not an allergic patient develops asthma.

  • 24.
    Moshkovits, I.
    et al.
    Tel Aviv Univ, Dept Clin Microbiol & Immunol, Sackler Fac Med, Tel Aviv, Israel..
    Reichman, H.
    Tel Aviv Univ, Dept Clin Microbiol & Immunol, Sackler Fac Med, Tel Aviv, Israel..
    Karo-Atar, D.
    Tel Aviv Univ, Dept Clin Microbiol & Immunol, Sackler Fac Med, Tel Aviv, Israel..
    Rozenberg, P.
    Tel Aviv Univ, Dept Clin Microbiol & Immunol, Sackler Fac Med, Tel Aviv, Israel..
    Zigmond, E.
    Tel Aviv Univ, Sourasky Med Ctr, Res Ctr Digest Tract & Liver Dis, Tel Aviv, Israel.;Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel..
    Haberman, Y.
    Cincinnati Childrens Hosp Med Ctr, Dept Gastroenterol Hepatol & Nutr, Cincinnati, OH 45229 USA.;Edmond & Lily Safra Childrens Hosp, Sheba Med Ctr, Div Pediat Gastroenterol Hepatol & Nutr, Tel Hashomer, Israel..
    Ben Baruch-Morgenstern, N.
    Tel Aviv Univ, Dept Clin Microbiol & Immunol, Sackler Fac Med, Tel Aviv, Israel..
    Lampinen, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Itan, M.
    Tel Aviv Univ, Dept Clin Microbiol & Immunol, Sackler Fac Med, Tel Aviv, Israel..
    Denson, L. A.
    Cincinnati Childrens Hosp Med Ctr, Dept Gastroenterol Hepatol & Nutr, Cincinnati, OH 45229 USA..
    Varol, C.
    Tel Aviv Univ, Sourasky Med Ctr, Res Ctr Digest Tract & Liver Dis, Tel Aviv, Israel.;Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel..
    Munitz, A.
    Tel Aviv Univ, Dept Clin Microbiol & Immunol, Sackler Fac Med, Tel Aviv, Israel..
    A key requirement for CD300f in innate immune responses of eosinophils in colitis2017In: Mucosal Immunology, ISSN 1933-0219, E-ISSN 1935-3456, Vol. 10, no 1, p. 172-183Article in journal (Refereed)
    Abstract [en]

    Eosinophils are traditionally studied in the context of type 2 immune responses. However, recent studies highlight key innate immune functions for eosinophils especially in colonic inflammation. Surprisingly, molecular pathways regulating innate immune activities of eosinophil are largely unknown. Wehave recently shown that the CD300f is highly expressed by colonic eosinophils. Nonetheless, the role of CD300f in governing innate immune eosinophil activities is ill-defined. RNA sequencing of 162 pediatric Crohn's disease patients revealed upregulation of multiple Cd300 family members, which correlated with the presence of severe ulcerations and inflammation. Increased expression of CD300 family receptors was also observed in active ulcerative colitis (UC) and in mice following induction of experimental colitis. Specifically, the expression of CD300f was dynamically regulated in monocytes and eosinophils. Dextran sodium sulfate (DSS)-treated Cd300f (-/-) mice exhibit attenuated disease activity and histopathology in comparison with DSS-treated wild type (WT). Decreased disease activity in Cd300f (-/-) mice was accompanied with reduced inflammatory cell infiltration and nearly abolished production of pro-inflammatory cytokines. Monocyte depletion and chimeric bone marrow transfer experiments revealed a cell-specific requirement for CD300f in innate immune activation of eosinophils. Collectively, we uncover a new pathway regulating innate immune activities of eosinophils, a finding with significant implications in eosinophil-associated gastrointestinal diseases.

  • 25.
    Venge, J
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lampinen, M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hakansson, L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Rak, S
    Venge, P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Identification of IL-5 and RANTES as the major eosinophils chemoattractants in the astmatic lung1996In: J Allergy Clin Immunol, Vol. 97, p. 1110-Article in journal (Refereed)
  • 26.
    Wagner, Michael
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lampinen, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sangfelt, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Agnarsdóttir, Margrét
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Budesonide Treatment of Patients With Collagenous Colitis Restores Normal Eosinophil and T-cell Activity in the Colon2010In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 16, no 7, p. 1118-1126Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to assess the activity of eosinophils, neutrophils and CD4+ as well as CD8+ T-cells in eleven patients with active collagenous colitis (CC) before and after eight weeks of budesonide treatment (9 mg once daily) compared to ten healthy individuals.

    Methods: Clinical symptoms were recorded and intestinal biopsy samples were taken and analysed by flow cytometry. Eosinophils with a high surface expression of CD44 and low CD9 expression were classified as activated. Neutrophil activity was assessed by their expression of CD66b and CD69 was used as an activation marker for T cells.

    Results: All patients responded to the treatment. The eosinophils in active CC showed increased activity compared to controls. The activity was back to control levels after treatment. Neutrophils were not activated in CC patients before or after treatment.

    CD8+ T cells from untreated CC patients had a lower activity than controls, and a tendency of lower activity was observed on CD4+ T cells. After treatment, the activity was increased on both types of T cells and was not different from controls.

    Conclusions: In the present study we demonstrated that the inflammation in CC is characterized by activated eosinophils but there is no neutrophil activity. CD4+ and CD8+ T cells are increased in numbers in active CC but, surprisingly, they had a lower grade of activity than in control subjects. The major finding in this study is that budesonide treatment restores the normal activation of eosinophils and T-cells, accompanied by clinical remission.

  • 27.
    Wagner, Michael
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Peterson, Christer GB
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stolt, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sangfelt, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Agnarsdottir, Margret
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lampinen, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Fecal eosinophil cationic protein as a marker of active disease and treatment outcome in collagenous colitis: A pilot study2011In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 46, no 7-8, p. 849-854Article in journal (Refereed)
    Abstract [en]

    Background and aims. Fecal calprotectin (FC) is used as a marker for intestinal inflammation in inflammatory bowel disease (IBD) but there is no reliable marker for collagenous colitis (CC). We have previously demonstrated that the mucosal inflammation in CC is characterized by eosinophil activation, which is restored during budesonide treatment, but there is no enhanced neutrophil activity. The aim of this study was to evaluate the use of fecal eosinophil cationic protein (F-ECP) and eosinophil protein X (F-EPX) compared with the neutrophil-derived myeloperoxidase (F-MPO) and FC in patients treated for active CC. Methods. Patients with active CC (n = 12) were studied before and after 3, 7, 28 and 56 days of budesonide treatment. Clinical symptoms and stool frequency were recorded, fecal samples were collected, and F-ECP, F-EPX, F-MPO and FC were measured at each occasion. Results. All but one patient achieved remission. On inclusion 92%, 67%, 67% and 75% of the patients had elevated F-ECP, F-EPX, F-MPO and FC levels, respectively. All markers decreased during the treatment, particularly F-ECP and F-EPX, which decreased after only 3 days. At the end of the study 100%, 92%, 83% and 75% of the patients had normal F-ECP, F-EPX, F-MPO and FC values, respectively. Conclusion. F-ECP demonstrated the best discriminating capacity in detecting active CC. A normalized F-ECP and F-EPX may further be studied as a marker for successful treatment. During budesonide treatment there is a rapid fall in F-ECP and F-EPX, accompanied by clinical improvement, indicating an essential role for the eosinophil participating in the pathophysiology of CC.

  • 28.
    Wagner, Michael
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Peterson, Christer G B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sangfelt, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lampinen, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Increased Fecal Levels of Chromogranin A, Chromogranin B and Secretoneurine in Collagenous Colitis2013In: Inflammation, ISSN 0360-3997, E-ISSN 1573-2576, Vol. 36, no 4, p. 855-861Article in journal (Refereed)
    Abstract [en]

    Interactions between the enteric nervous system and the immune system are suggested to play an important role in the pathophysiology of inflammatory bowel disease (IBD). This study aims to determine if chromogranin A (CgA), chromogranin B (CgB), and secretoneurin (SN) are detectable in feces (F) from patients with collagenous colitis (CC) and to compare the levels found in patients with ulcerative colitis (UC) and Crohn’s disease (CD) before and during treatment. Patients with CC (n = 12) were studied before and after 3, 7, 28, and 56 days of treatment. Patients with IBD (UC, n = 21; CD, n = 11) were studied before and after 28 and 56 days of treatment. Clinical data were recorded, and fecal samples were collected at each occasion. F-CgA, F-CgB, and F-SN were measured by RIA. Eleven patients with CC, 21 with UC, and 10 with CD achieved remission. On inclusion, CC patients had higher levels of F-CgA, F-CgB, and F-SN than patients with IBD and controls. Patients with IBD expressed markedly lower levels of F-SN than controls. During treatment, F-SN in CC patients decreased to control levels but remained low in IBD patients. No change was found in F-CgA or F-CgB in any of the groups. In conclusion, CgA, CgB, and SN are detectable in feces, and CC patients express higher values than patients with IBD and controls. During treatment, F-SN decreased to control levels in CC. These findings suggest that the enteric nervous system is clearly involved in the pathophysiology of CC.

  • 29. Wallon, Conny
    et al.
    Persborn, Mats
    Jönsson, Maria
    Wang, Arthur
    Phan, Van
    Lampinen, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Vicario, Maria
    Santos, Javier
    Sherman, Philip M.
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ericson, Ann-Charlott
    McKay, Derek M.
    Söderholm, Johan D.
    Eosinophils Express Muscarinic Receptors and Corticotropin-Releasing Factor to Disrupt the Mucosal Barrier in Ulcerative Colitis2011In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 140, no 5, p. 1597-1607Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Altered intestinal barrier function has been implicated in the pathophysiology of ulcerative colitis (UC) in genetic, functional, and epidemiological studies. Mast cells and corticotropinreleasing factor (CRF) regulate the mucosal barrier in human colon. Because eosinophils are often increased in colon tissues of patients with UC, we assessed interactions among mast cells, CRF, and eosinophils in the mucosal barrier of these patients. METHODS: Transmucosal fluxes of protein antigens (horseradish peroxidase) and paracellular markers (51Cr-EDTA, fluorescein isothiocyanate-dextran 4000) were studied in noninflamed, colonic mucosal biopsy samples collected from 26 patients with UC and 53 healthy volunteers (controls); samples were mounted in Ussing chambers. We also performed fluorescence and electron microscopy of human tissue samples, assessed isolated eosinophils, and performed mechanistic studies using in vitro cocultured eosinophils (15HL-60), mast cells (HMC-1), and a colonic epithelial cell line (T84). RESULTS: Colon tissues from patients with UC had significant increases in permeability to protein antigens compared with controls. Permeability was blocked by atropine (a muscarinic receptor antagonist), alpha-helical CRF(9-41) (a CRF receptor antagonist), and lodoxamide (a mast-cell stabilizer). Eosinophils were increased in number in UC tissues (compared with controls), expressed the most M2 and M3 muscarinic receptors of any mucosal cell type, and had immunoreactivity to CRF. In coculture studies, carbachol activation of eosinophils caused production of CRF and activation of mast cells, which increased permeability of T84 epithelial cells to macromolecules. CONCLUSIONS: We identified a neuroimmune intercellular circuit (from cholinergic nerves, via eosinophils to mast cells) that mediates colonic mucosal barrier dysfunction in patients with UC. This circuit might exacerbate mucosal inflammation.

1 - 29 of 29
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf