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Liu, J., Fu, Z., Hellman, L. & Svärd, S. G. (2019). Cleavage specificity of recombinant Giardia intestinalis cysteine proteases: Degradation of immunoglobulins and defensins. Molecular and biochemical parasitology (Print), 227, 29-38
Open this publication in new window or tab >>Cleavage specificity of recombinant Giardia intestinalis cysteine proteases: Degradation of immunoglobulins and defensins
2019 (English)In: Molecular and biochemical parasitology (Print), ISSN 0166-6851, E-ISSN 1872-9428, Vol. 227, p. 29-38Article in journal (Refereed) Published
Abstract [en]

Giardia intestinalis is a protozoan parasite and the causative agent of giardiasis, a common diarrheal disease. Cysteine protease (CP) activities have been suggested to be involved in Giardia's pathogenesis and we have recently identified and characterized three secreted Giardia CPs; CP14019, CP16160 and CP16779. Here we have studied the cleavage specificity of these CPs using substrate phage display and recombinant protein substrates. The phage display analyses showed that CP16160 has both chymase and tryptase activity and a broad substrate specificity. This was verified using recombinant protein substrates containing different variants of the cleavage sites. Phage display analyses of CP14019 and CP16779 failed but the substrate specificity of CP14019 and CP16779 was tested using the recombinant substrates generated for CP16160. CP16160 and CP14019 showed similar substrate specificity, while CP16779 has a slightly different substrate specificity. The consensus sequence for cleavage by CP16160, obtained from phage display analyses, was used in an in silico screen of the human intestinal proteome for detection of potential targets. Immunoglobulins, including IgA and IgG and defensins (α-HD6 and β-HD1) were predicted to be targets and they were shown to be cleaved by the recombinant CPs in vitro. Our results suggest that the secreted Giardia CPs are key players in the interaction with host cells during Giardia infections since they can cleave several components of the human mucosal defense machinery.

Keywords
Cysteine protease, Defensins, Diarrhea, Immunoglobulins, Parasite, Phage display
National Category
Microbiology
Identifiers
urn:nbn:se:uu:diva-372982 (URN)10.1016/j.molbiopara.2018.10.004 (DOI)000457660900006 ()30458129 (PubMedID)
Funder
Swedish Research Council, 2017-02918
Available from: 2019-01-10 Created: 2019-01-10 Last updated: 2019-03-05Bibliographically approved
Fu, Z., Akula, S., Thorpe, M., Chahal, G., de Garavilla, L., Kervinen, J. & Hellman, L. (2019). Extended cleavage specificity of sheep mast cell protease-2: A classical chymase with preference to aromatic P1 substrate residues. Developmental and Comparative Immunology, 92, 160-169
Open this publication in new window or tab >>Extended cleavage specificity of sheep mast cell protease-2: A classical chymase with preference to aromatic P1 substrate residues
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2019 (English)In: Developmental and Comparative Immunology, ISSN 0145-305X, E-ISSN 1879-0089, Vol. 92, p. 160-169Article in journal (Refereed) Published
Abstract [en]

Serine proteases constitute the major protein content of mammalian mast cell granules and the selectivity for substrates by these proteases is of major importance for the role of mast cells in immunity. In order to address this subject, we present here the extended cleavage specificity of sheep mast cell protease-2 (MCP2), a chymotrypsin-type serine protease. Comparison of the extended specificity results to a panel of mammalian mast cell chymases show, in almost all aspects, the same cleavage characteristics. This includes preference for aromatic residues (Phe, Tyr, Trp) in the P1 position of substrates and a preference for aliphatic residues in most other substrate positions around the cleavage site. MCP2 also cleaved, albeit relatively low efficiency, after Leu in the P1 position. In contrast to the human, mouse, hamster and opossum chymases that show a relatively strong preference for negatively charged amino acids in the P2'position, the sheep MCP2, however, lacked that preference. Therefore, together with the rat chymase (rMCP1), sheep MCP2 can be grouped to a small subfamily of mammalian chymases that show fairly unspecific preference in the P2'position. In summary, the results here support the view of a strong evolutionary conservation of a potent chymotrypsin-type protease as a key feature of mammalian mast cells.

Place, publisher, year, edition, pages
ELSEVIER SCI LTD, 2019
Keywords
Mast cell, Chymase, Sheep, Cleavage specificity, Animal model
National Category
Immunology Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-378627 (URN)10.1016/j.dci.2018.11.019 (DOI)000458596200017 ()30481523 (PubMedID)
Funder
Swedish Research Council
Available from: 2019-03-11 Created: 2019-03-11 Last updated: 2019-03-11Bibliographically approved
Thorpe, M., Fu, Z., Albat, E., Akula, S., de Garavilla, L., Kervinen, J. & Hellman, L. (2018). Extended cleavage specificities of mast cell proteases 1 and 2 from golden hamster: Classical chymase and an elastolytic protease comparable to rat and mouse MCP-5. PLoS ONE, 13(12), Article ID e0207826.
Open this publication in new window or tab >>Extended cleavage specificities of mast cell proteases 1 and 2 from golden hamster: Classical chymase and an elastolytic protease comparable to rat and mouse MCP-5
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2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 12, article id e0207826Article in journal (Refereed) Published
Abstract [en]

Serine proteases constitute the major protein content of mast cell secretory granules. Here we present the extended cleavage specificity of two such proteases from the golden hamster, Mesocricetus auratus. Analysis by phage display technique showed that one of them (HAM1) is a classical chymase with a specificity similar to the human mast cell chymase. However, in contrast to the human chymase, it does not seem to have a particular preference for any of the three aromatic amino acids, Phe, Tyr and Trp, in the P1 position of substrates. HAM1 also efficiently cleaved after Leu similarly to human and many other mast cell chymases. We observed only a 3-fold lower cleavage activity on Leu compared to substrates with P1 aromatic amino acids. Chymotryptic enzymes seem to be characteristic for connective tissue mast cells in mammalian species from opossums to humans, which indicates a very central role of these enzymes in mast cell biology. HAM1 also seems to have the strongest preference for negatively charged amino acids in the P2 position of all mast cell chymases so far characterized. The second hamster chymase, HAM2, is an elastolytic in its activity, similarly to the alpha-chymases in rats and mice (rMCP-5 and mMCP-5, respectively). The presence of an alpha-chymase that developed elastase activity thereby seems to be a relatively early modification of the alpha-chymase within the rodent branch of the mammalian evolutionary tree.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE, 2018
National Category
Immunology Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-373000 (URN)10.1371/journal.pone.0207826 (DOI)000452307600021 ()30521603 (PubMedID)
Funder
Swedish Research Council, 621-2011-5007
Available from: 2019-01-14 Created: 2019-01-14 Last updated: 2019-01-14Bibliographically approved
Thorpe, M., Fu, Z., Chahal, G., Akula, S., Kervinen, J., de Garavilla, L. & Hellman, L. (2018). Extended cleavage specificity of human neutrophil cathepsin G: A low activity protease with dual chymase and tryptase-type specificities. PLoS ONE, 13(4), Article ID e0195077.
Open this publication in new window or tab >>Extended cleavage specificity of human neutrophil cathepsin G: A low activity protease with dual chymase and tryptase-type specificities
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2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 4, article id e0195077Article in journal (Refereed) Published
Abstract [en]

Human neutrophils express at least four active serine proteases, cathepsin G, N-elastase, proteinase 3 and neutrophil serine protease 4 (NSP4). They have all been extensively studied due to their importance in neutrophil biology and immunity. However, their extended cleavage specificities have never been determined in detail. Here we present a detailed cleavage specificity analysis of human cathepsin G (hCG). The specificity was determined by phage display analysis and the importance of individual amino acids in and around the cleavage site was then validated using novel recombinant substrates. To provide a broader context to this serine protease, a comparison was made to the related mast cell protease, human chymase (HC). hCG showed similar characteristics to HC including both the primary and extended specificities. As expected, Phe, Tyr, Trp and Leu were preferred in the P1 position. In addition, both proteases showed a preference for negatively charged amino acids in the P2 A position of substrates and a preference for aliphatic amino acids both upstream and downstream of the cleavage site. However, overall the catalytic activity of hCG was similar to 10-fold lower than HC. hCG has previously been reported to have a dual specificity consisting of chymase and tryptase-type activities. In our analysis, tryptase activity against substrates with Lys in P1 cleavage position was indeed only 2-fold less efficient as compared to optimal chymase substrates supporting strong dual-type specificity. We hope the information presented here on extended cleavage specificities of hCG and HC will assist in the search for novel in vivo substrates for these proteases as well as aid in the efforts to better understand the role of hCG in immunity and bacterial defence.

National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-353202 (URN)10.1371/journal.pone.0195077 (DOI)000430026900017 ()29652924 (PubMedID)
Funder
Swedish Research Council, 621-2011-5007
Available from: 2018-06-13 Created: 2018-06-13 Last updated: 2018-06-13Bibliographically approved
Fu, Z., Thorpe, M., Akula, S., Chahal, G. & Hellman, L. (2018). Extended Cleavage Specificity of Human Neutrophil Elastase, Human Proteinase 3, and Their Distant Ortholog Clawed Frog PR3-Three Elastases With Similar Primary but Different Extended Specificities and Stability. Frontiers in Immunology, 9, Article ID 2387.
Open this publication in new window or tab >>Extended Cleavage Specificity of Human Neutrophil Elastase, Human Proteinase 3, and Their Distant Ortholog Clawed Frog PR3-Three Elastases With Similar Primary but Different Extended Specificities and Stability
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2018 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 9, article id 2387Article in journal (Refereed) Published
Abstract [en]

Serine proteases are major granule constituents of several of the human hematopoietic cell lineages. Four proteolytically active such proteases have been identified in human neutrophils: cathepsin G (hCG), N-elastase (hNE), proteinase 3 (hPR-3), and neutrophil serine protease 4 (hNSP-4). Here we present the extended cleavage specificity of two of the most potent and most abundant of these enzymes, hNE and hPR-3. Their extended specificities were determined by phage display and by the analysis of a panel of chromogenic and recombinant substrates. hNE is an elastase with a relatively broad specificity showing a preference for regions containing several aliphatic amino acids. The protease shows self-cleaving activity, which results in the loss of activity during storage even at +4 degrees C. Here we also present the extended cleavage specificity of hPR-3. Compared with hNE, it shows considerably lower proteolytic activity. However, it is very stable, shows no self-cleaving activity and is actually more active in the presence of SDS, possibly by enhancing the accessibility of the target substrate. This enables specific analysis of hPR-3 activity even in the presence of all the other neutrophil enzymes with addition of 1% SDS. Neutrophils are the most abundant white blood cell in humans and one of the key players in our innate immune defense. The neutrophil serine proteases are very important for the function of the neutrophils and therefore also interesting from an evolutionary perspective. In order to study the origin and functional conservation of these neutrophil proteases we have identified and cloned an amphibian ortholog, Xenopus PR-3 (xPR-3). This enzyme was found to have a specificity very similar to hPR-3 but did not show the high stability in the presence of SDS. The presence of an elastase in Xenopus closely related to hPR-3 indicates a relatively early appearance of these enzymes during vertebrate evolution.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA, 2018
Keywords
neutrophilic granulocyte, serine protease, hematopoiesis, proteinase 3, N-elastase, amphibian, neutropenia, phage display
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-368440 (URN)10.3389/fimmu.2018.02387 (DOI)000447372500001 ()
Funder
Swedish Research Council, 621-2011-5007
Available from: 2018-12-10 Created: 2018-12-10 Last updated: 2018-12-10Bibliographically approved
Liu, J., Ma'ayeh, S. Y., Peirasmaki, D., Lundstrom-Stadelmann, B., Hellman, L. & Svärd, S. G. (2018). Secreted Giardia intestinalis cysteine proteases disrupt intestinal epithelial cell junctional complexes and degrade chemokines. Virulence, 9(1), 879-894
Open this publication in new window or tab >>Secreted Giardia intestinalis cysteine proteases disrupt intestinal epithelial cell junctional complexes and degrade chemokines
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2018 (English)In: Virulence, ISSN 2150-5594, E-ISSN 2150-5608, Vol. 9, no 1, p. 879-894Article in journal (Refereed) Published
Abstract [en]

Giardiasis is a common diarrheal disease caused by the protozoan parasite Giardia intestinalis. Cysteine proteases (CPs) are acknowledged as virulence factors in Giardia but their specific role in the molecular pathogenesis of disease is not known. Herein, we aimed to characterize the three main secreted CPs (CP14019, CP16160 and CP16779), which were identified by mass spectrometry in the medium during interaction with intestinal epithelial cells (IECs) in vitro. First, the CPs were epitope-tagged and localized to the endoplasmic reticulum and cytoplasmic vesicle-like structures. Second, we showed that recombinant CPs, expressed in Pichia pastoris, are more active in acidic environment (pH 5.5-6) and we determined the kinetic parameters using fluorogenic substrates. Third, excretory-secretory proteins (ESPs) from Giardia trophozoites affect the localization of apical junctional complex (AJC) proteins and recombinant CPs cleave or re-localize the AJC proteins (claudin-1 and -4, occludin, JAM-1, beta-catenin and E-cadherin) of IECs. Finally, we showed that the ESPs and recombinant CPs can degrade several chemokines, including CXCL1, CXCL2, CXCL3, IL-8, CCL2, and CCL20, which are up-regulated in IECs during Giardia-host cell interactions. This is the first study that characterizes the role of specific CPs secreted from Giardia and our results collectively indicate their roles in the disruption of the intestinal epithelial barrier and modulating immune responses during Giardia infections.

Keywords
parasite, diarrhea, tight junction, chemokine, intestinal barrier, secretion, cathepsin B, Host-pathogen interactions
National Category
Infectious Medicine Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-355478 (URN)10.1080/21505594.2018.1451284 (DOI)000431949700001 ()29726306 (PubMedID)
Funder
Swedish Research Council, 2012-03364
Available from: 2018-06-29 Created: 2018-06-29 Last updated: 2019-01-10Bibliographically approved
Saupe, F., Reichel, M., Huijbers, E. J. M., Femel, J., Markgren, P.-O., Andersson, C. E., . . . Olsson, A.-K. (2017). Development of a novel therapeutic vaccine carrier that sustains high antibody titers against several targets simultaneously. The FASEB Journal, 31(3), 1204-1214
Open this publication in new window or tab >>Development of a novel therapeutic vaccine carrier that sustains high antibody titers against several targets simultaneously
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2017 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 31, no 3, p. 1204-1214Article in journal (Refereed) Published
Abstract [en]

With the aim to improve the efficacy of therapeutic vaccines that target self-antigens, we have developed a novel fusion protein vaccine on the basis of the C-terminal multimerizing end of the variable lymphocyte receptor B (VLRB), the Ig equivalent in jawless fishes. Recombinant vaccines were produced in Escherichia coli by fusing the VLRB sequence to 4 different cancer-associated target molecules. The anti-self-immune response generated in mice that were vaccinated with VLRB vaccines was compared with the response in mice that received vaccines that contained bacterial thioredoxin (TRX), previously identified as an efficient carrier. The anti-self-Abswere analyzed with respect to titers, binding properties, and duration of response. VLRB-vaccinatedmice displayed a 2-to 10-fold increase in anti-self-Ab titers and a substantial decrease in Abs against the foreign part of the fusion protein compared with the response in TRX-vaccinated mice (P < 0.01). VLRB-generated Ab response had duration similar to the corresponding TRX-generatedAbs, but displayed a higher diversity in binding characteristics. Of importance, VLRB vaccines could sustain an immune response against several targets simultaneously. VLRB vaccines fulfill several key criteria for an efficient therapeutic vaccine that targets self-antigens as a result of its small size, its multimerizing capacity, and nonexposed foreign sequences in the fusion protein.- Saupe, F., Reichel, M., Huijbers, E. J. M., Femel, J., Markgren, P.- O., Andersson, C. E., Deindl, S., Danielson, U. H., Hellman, L. T., Olsson, A.- K. Development of a novel therapeutic vaccine carrier that sustains high antibody titers against several targets simultaneously.

Keywords
cancer, VLRB, tolerance, ED-A, ED-B
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-320668 (URN)10.1096/fj.201600820R (DOI)000395671200032 ()27993994 (PubMedID)
Note

De 2 sista författarna delar sistaförfattarskapet.

Available from: 2017-06-07 Created: 2017-06-07 Last updated: 2017-06-07Bibliographically approved
Fu, Z., Thorpe, M., Alemayehu, R., Roy, A., Kervinen, J., de Garavilla, L., . . . Hellman, L. (2017). Highly Selective Cleavage of Cytokines and Chemokines by the Human Mast Cell Chymase and Neutrophil Cathepsin G. Journal of Immunology, 198(4), 1474-1483
Open this publication in new window or tab >>Highly Selective Cleavage of Cytokines and Chemokines by the Human Mast Cell Chymase and Neutrophil Cathepsin G
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2017 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 198, no 4, p. 1474-1483Article in journal (Refereed) Published
Abstract [en]

Human mast cell chymase (HC) and human neutrophil cathepsin G (hCG) show relatively similar cleavage specificities: they both have chymotryptic activity but can also cleave efficiently after leucine. Their relatively broad specificity suggests that they may cleave almost any substrate if present in high enough concentrations or for a sufficiently long time. A number of potential substrates have been identified for these enzymes and, recently, these enzymes have also been implicated in regulating cytokine activity by cleaving numerous cytokines and chemokines. To obtain a better understanding of their selectivity for various potential in vivo substrates, we analyzed the cleavage of a panel of 51 active recombinant cytokines and chemokines. Surprisingly, our results showed a high selectivity of HC; only 4 of 51 of these proteins were substantially cleaved. hCG cleaved a few additional proteins, although this occurred after adding almost equimolar amounts of enzyme to target. The explanation for this wide difference in activity against peptides or other linear substrates compared with native proteins is most likely related to the reduced accessibility of the enzymes to potential cleavage sites in folded proteins. In this article, we present evidence that sites not exposed on the surface of the protein are not cleaved by the enzyme. Interestingly, both enzymes readily cleaved IL-18 and IL-33, two IL-1-related alarmins, as well as the cytokine IL-15, which is important for T cell and NK cell homeostasis. Cleavage of the alarmins by HC and hCG suggests a function in regulating excessive inflammation.

Place, publisher, year, edition, pages
AMER ASSOC IMMUNOLOGISTS, 2017
National Category
Immunology
Identifiers
urn:nbn:se:uu:diva-320461 (URN)10.4049/jimmunol.1601223 (DOI)000395898600011 ()28053237 (PubMedID)
Available from: 2017-04-26 Created: 2017-04-26 Last updated: 2017-04-26Bibliographically approved
Akula, S. & Hellman, L. (2017). The Appearance and Diversification of Receptors for IgM During Vertebrate Evolution. In: Kubagawa, H Burrows, PD (Ed.), IGM AND ITS RECEPTORS AND BINDING PROTEINS: (pp. 1-23). SPRINGER-VERLAG BERLIN
Open this publication in new window or tab >>The Appearance and Diversification of Receptors for IgM During Vertebrate Evolution
2017 (English)In: IGM AND ITS RECEPTORS AND BINDING PROTEINS / [ed] Kubagawa, H Burrows, PD, SPRINGER-VERLAG BERLIN , 2017, p. 1-23Chapter in book (Refereed)
Abstract [en]

Three different receptors that interact with the constant domains of IgM have been identified: the polymeric immunoglobulin (Ig) receptor (PIGR), the dual receptor for IgA/IgM (Fc alpha mu R) and the IgM receptor (Fc mu R). All of them are related in structure and located in the same chromosomal region in mammals. The functions of the PIGRs are to transport IgM and IgA into the intestinal lumen and to saliva and tears, whereas the Fc alpha mu Rs enhance uptake of immune complexes and antibody coated bacteria and viruses by B220+ B cells and phagocytes, as well as dampening the Ig response to thymus-independent antigens. The Fc mu Rs have broad-spectrum effects on B-cell development including effects on IgM homeostasis, B-cell survival, humoral immune responses and also in autoantibody formation. The PIGR is the first of these receptors to appear during vertebrate evolution and is found in bony fish and all tetrapods but not in cartilaginous fish. The Fc mu R is present in all extant mammalian lineages and also in the Chinese and American alligators, suggesting its appearance with early reptiles. Currently the Fc alpha mu R has only been found in mammals and is most likely the evolutionary youngest of the three receptors. In bony fish, the PIGR has either 2, 3, 4, 5 or 6 extracellular Ig-like domains, whereas in amphibians, reptiles and birds it has 4 domains, and 5 in all mammals. The increase in domain number from 4 to 5 in mammals has been proposed to enhance the interaction with IgA. Both the Fc alpha mu Rs and the Fc mu Rs contain only one Ig domain; the domain that confers Ig binding. In both of these receptors this domain shows the highest degree of sequence similarity to domain 1 of the PIGR. All Ig domains of these three receptors are V type domains, indicating they all have the same origin although they have diversified extensively in function during vertebrate evolution by changing expression patterns and cytoplasmic signaling motifs.

Place, publisher, year, edition, pages
SPRINGER-VERLAG BERLIN, 2017
Series
Current Topics in Microbiology and Immunology, ISSN 0070-217X ; 408
National Category
Microbiology
Identifiers
urn:nbn:se:uu:diva-346586 (URN)10.1007/82_2017_22 (DOI)000413935700002 ()28884191 (PubMedID)978-3-319-64526-1 (ISBN)978-3-319-64524-7 (ISBN)
Available from: 2018-03-20 Created: 2018-03-20 Last updated: 2018-03-20Bibliographically approved
Hellman, L. T., Akula, S., Thorpe, M. & Fu, Z. (2017). Tracing the Origins of IgE, Mast Cells, and Allergies by Studies of Wild Animals. Frontiers in Immunology, 8, Article ID 1749.
Open this publication in new window or tab >>Tracing the Origins of IgE, Mast Cells, and Allergies by Studies of Wild Animals
2017 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 8, article id 1749Article, review/survey (Refereed) Published
Abstract [en]

In most industrialized countries, allergies have increased in frequency quite dramatically during the past 50 years. Estimates show that 20-30% of the populations are affected. Allergies have thereby become one of the major medical challenges of the twenty-first century. Despite several theories including the hygiene hypothesis, there are still very few solid clues concerning the causes of this increase. To trace the origins of allergies, we have studied cells and molecules of importance for the development of IgE-mediated allergies, including the repertoire of immunoglobulin genes. These studies have shown that IgE and IgG most likely appeared by a gene duplication of IgY in an early mammal, possibly 220-300 million years ago. Receptors specific for IgE and IgG subsequently appeared in parallel with the increase in Ig isotypes from a subfamily of the recently identified Fc receptor-like molecules. Circulating IgE levels are generally very low in humans and laboratory rodents. However, when dogs and Scandinavian wolfs were analyzed, IgE levels were found to be 100-200 times higher compared to humans, indicating a generally much more active IgE synthesis in free-living animals, most likely connected to intestinal parasite infections. One of the major effector molecules released upon IgEmediated activation by mast cells are serine proteases. These proteases, which belong to the large family of hematopoietic serine proteases, are extremely abundant and can account for up to 35% of the total cellular protein. Recent studies show that several of these enzymes, including the chymases and tryptases, are old. Ancestors for these enzymes were most likely present in an early mammal more than 200 million years ago before the separation of the three extant mammalian lineages; monotremes, marsupials, and placental mammals. The aim is now to continue these studies of mast cell biology and IgE to obtain additional clues to their evolutionary conserved functions. A focus concerns why the humoral immune response involving IgE and mast cells have become so dysregulated in humans as well as several of our domestic companion animals.

Keywords
IgE, Fc receptor, mast cell, IgE homeostasis, allergy, dermatitis, asthma
National Category
Immunology Immunology in the medical area Microbiology in the medical area Microbiology
Identifiers
urn:nbn:se:uu:diva-347713 (URN)10.3389/fimmu.2017.01749 (DOI)000418285800001 ()29312297 (PubMedID)
Funder
Swedish Research Council, 621-2011-5007
Available from: 2018-04-06 Created: 2018-04-06 Last updated: 2018-04-06Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-1459-3815

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