Mast cells are best known for their role in
allergic reactions but are also now recognized for their important contributions to a number of disparate inflammatory conditions through the release of inflammatory mediators,
serglycin and other
proteoglycans, and
proteases. Because these tissue resident inflammatory cells express
proteases in such great abundance and their enzymatic activity results in cleavage of a multitude of
proteins and
peptides, which in turn modify tissue function, their substrate specificity, tissue distribution, and mode of action have become the subjects of great interest. Although mast cell
protease-dependent proteolysis is critical to host defense against invading pathogens, regulation of these hydrolytic
enzymes is essential to limiting self-induced damage as well. Indeed, dysregulated release of mast cell
proteases is now recognized to contribute to the pathogenesis of a number of inflammatory conditions including
asthma,
abdominal aortic aneurysm formation, vessel damage in
atherosclerosis and
hypertension,
arthritis, and
ischemia/reperfusion injury. Understanding how mast cell
proteases contribute to
inflammation will thus help unravel molecular mechanisms that underlie such immunologic disorders and will help identify new therapeutic targets for drug development.