Mast cell tryptase, a still enigmatic enzyme.
Tryptases constitute a subfamily of trypsin-like proteinases, stored in the mast cell secretory granules of all mammalian organisms. These enzymes are released along with other mediators into the extracellular medium upon mast cell activation/degranulation. Among the trypsin-like enzymes, tryptases are unique: they are present as active enzymes in the mast cell granules, but display activity only extracellularly, and have a specificity which is much more restricted than trypsin. Tryptases are mostly tetrameric, and in only few organisms (not in humans) are they inhibited by endogenous inhibitors in vitro. The enzymatic and molecular properties of tryptases are far better characterized that any of their plausible biological functions. On the basis of its structural and functional features it could be predicted that tryptase would not degrade a large number of proteins in vivo due to low accessibility to the tetramer central pore where the active sites face inwards. Although their biological function has not yet been clarified, tryptases seem to be involved in a number of mast cell-mediated allergic and inflammatory diseases. In particular, the involvement of tryptase in asthma, an inflammatory disease of the airways often caused by allergy, has been proposed. Here we review the present knowledge on the structure-function relationship of tryptases from different organisms, with special emphasis on human enzymes, and on their role in a variety of pathophysiological processes.
Fiorucci
L
L
Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Università di Roma Tor Vergata, via Montpellier 1, 00133, Rome, Italy.
Ascoli
F
F
D000818:Animals; D019143:Evolution, Molecular; D006801:Humans; D006967:Hypersensitivity; D018836:Inflammation Mediators; D008407:Mast Cells / Q000201:enzymology*; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D053802:Tryptases
D018836:Inflammation Mediators; D012697:Serine Endopeptidases; D053802:Tryptases