Waern, Ida
(2012).
The role of mast cell proteases in allergic disease and apoptosis.
Diss. (sammanfattning/summary)
Uppsala :
Sveriges lantbruksuniv.,
Acta Universitatis Agriculturae Sueciae, 1652-6880
; 2012:50
ISBN 978-91-576-7697-9
[Doctoral thesis]
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Abstract
Mast cells (MCs) are key effector cells in allergic reactions, through the release of a wide variety of granule-stored and de novo synthesized inflammatory mediators. The MC secretory granules contain exceedingly high levels of serglycin proteoglycan and the heparin-binding proteases chymase, tryptase and carboxypeptidase A.
In this thesis the contribution of mouse mast cell protease (mMCP)-4, which is thought to be the functional homolog to the human chymase, was studied in the context of allergic airway inflammation. Using two models of allergic airway inflammation, wild-type (WT) and mMCP-4 deficient (mMCP-4-/-) mice were treated with ovalbumin (OVA) or with house dust mite (HDM) extract. We found that the OVA challenged mMCP-4-/- mice displayed increased airway hyperreactivity and lung eosinophilia and in the HDM model they displayed increased serum IgE levels. Moreover, the level of IL-33, a pro-inflammatory cytokine, was enhanced in the lung tissue in mMCP-4-/- mice compared to WT mice after HDM-treatment.
The active proteases stored in MC granules have the ability to cleave a number of components upon degranulation. We could demonstrate that proteolytic degradation of IL-13 by MCs is mediated by a serine protease, dependent on serglycin proteoglycan for its storage.
Permeabilization of lysosomal membranes often leads to apoptosis and the released proteases take part in this process, activating pro-apoptotic compounds. We have found that serglycin-/- MCs are more resistant to apoptosis induced by secretory granule damage. We showed that serglycin-/- MCs exhibited reduced caspase-3 activity and protease activity in the cytosol compared to WT cells.
Taken together, the studies in this thesis suggest that MCs chymase plays a protective role in the development of allergic airway inflammation and this could possibly be explained by chymases ability to degrade the pro-inflammatory cytokine, IL-33. In addition, we also suggest that serglycin proteoglycan and serglycin-dependent MC proteases participate in IL-13 degradation as well as in MC apoptosis induced by secretory granule damage.
Authors/Creators: | Waern, Ida | ||||||||||
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Title: | The role of mast cell proteases in allergic disease and apoptosis | ||||||||||
Series Name/Journal: | Acta Universitatis Agriculturae Sueciae | ||||||||||
Year of publishing : | 2012 | ||||||||||
Number: | 2012:50 | ||||||||||
Number of Pages: | 66 | ||||||||||
Papers/manuscripts: |
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Place of Publication: | Uppsala | ||||||||||
Publisher: | Dept. of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences | ||||||||||
ISBN for printed version: | 978-91-576-7697-9 | ||||||||||
ISSN: | 1652-6880 | ||||||||||
Language: | English | ||||||||||
Publication Type: | Doctoral thesis | ||||||||||
Full Text Status: | Public | ||||||||||
Agris subject categories.: | X Agricola extesions > X30 Life sciences | ||||||||||
Subjects: | (A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Biochemistry and Molecular Biology (A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Cell Biology (A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Immunology (Immunology in the medical area to be 30110) (A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science > Medical Bioscience | ||||||||||
Agrovoc terms: | mast cells, proteases, proteoglycans, human diseases, asthma, hypersensitivity, apoptosis | ||||||||||
Keywords: | mast cells, serglycin proteoglycan, protease, chymase, allergic airway inflammation, asthma, apoptosis | ||||||||||
URN:NBN: | urn:nbn:se:slu:epsilon-e-607 | ||||||||||
Permanent URL: | http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-e-607 | ||||||||||
ID Code: | 9026 | ||||||||||
Department: | (VH) > Dept. of Anatomy, Physiology and Biochemistry | ||||||||||
Deposited By: | Ida Waern | ||||||||||
Deposited On: | 06 Sep 2012 13:21 | ||||||||||
Metadata Last Modified: | 02 Dec 2014 10:51 |
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