The role of mast cell proteases in allergic disease and apoptosis

摘要: Mast cells (MCs) are key effector in allergic reactions, through the release of a wide variety granule-stored and de novo synthesized inflammatory mediators. The MC secretory granules contain exceedingly high levels serglycin proteoglycan heparin-binding proteases chymase, tryptase carboxypeptidase A. In this thesis contribution mouse mast cell protease (mMCP)-4, which is thought to be functional homolog human was studied context airway inflammation. Using two models inflammation, wild-type (WT) mMCP-4 deficient (mMCP-4-/-) mice were treated with ovalbumin (OVA) or house dust mite (HDM) extract. We found that OVA challenged mMCP-4-/- displayed increased hyperreactivity lung eosinophilia HDM model they serum IgE levels. Moreover, level IL-33, pro-inflammatory cytokine, enhanced tissue compared WT after HDM-treatment. The active stored have ability cleave number components upon degranulation. could demonstrate proteolytic degradation IL-13 by MCs mediated serine protease, dependent on for its storage. Permeabilization lysosomal membranes often leads apoptosis released take part process, activating pro-apoptotic compounds. serglycin-/- more resistant induced granule damage. showed exhibited reduced caspase-3 activity cytosol cells. Taken together, studies suggest chymase plays protective role development inflammation possibly explained chymases degrade IL-33. addition, we also serglycin-dependent participate as well