MATRIX METALLOPROTEINOSES IN IMMUNITY

Matrix metalloproteinases (MMPs) are a family of zinc-containing endo- proteinases that share structural domains but differ in substrate spec ificity, cellular sources, and inducibility. Macrophage production and secretion of large quantities of many MMPs, after contact with matrix proteins, is enhanced by surface determinants on activated T cells an d suppressed by cytokines from Th1 and Th2 cells. T cells secrete pred ominantly the gelatinases MMP-2 and -9, after beta(1) integrin- or vas cular cell adhesion molecule (VCAM)-1-dependent stimulation by cytokin es and inflammatory mediators. MMPs of both T cells and macrophages fa cilitate secretion of TNF-alpha, by cleavage of the membrane-bound for m. T cell MMPs prepare connective tissue matrices for T cell chemotaxi s across basement membranes and through tissues. The greater amounts o f diverse MMPs from macrophages are capable of degrading connective ti ssues, which may release stored growth factors. In limited studies of animal models of autoimmunity, specific MMP inhibitors have significan tly decreased edema and inflammatory tissue damage, suggesting possibl e therapeutic benefits.