Matrix metalloproteases and lung disease.

Development, tissue remodelling, cell migra- tion, inflammation, angiogenesis, and wound healing are just some of the physiological pro- cesses in which the matrix metalloproteases (MMPs), a family of highly homologous endo- peptidases, play a crucial part.'" Collectively the MMPs can cleave most, if not all, the protein constituents of the extracellular matrix including collagen, proteoglycan, laminin, fibronectin, and elastin. In so doing they facilitate cell movement, reorientation, and dispersal. The production and action of the MMPs are subject to strict control, ensuring limited proteolysis of the extracellular matrix during cell migration, tissue remodelling and repair."' Inadequate regulation of MMP production or action has, however, been implicated in a wide range of pathological processes including several lung diseases, rheumatoid arthritis, periodontal and renal diseases, osteoarthritis, fibrotic disorders, and tumour invasion. 7-12 Recent studies elucidating (1) the sequence homologies between members of the MMP family,'3 (2) factors involved in the regulation of MMP expression,'4 15 and (3) mechanisms of MMP activation and inhibition'6 17 have added considerably to our knowledge of the crucial control mechanisms which can tip the balance of MMP action from normal homoeostasis to pathological process. In this review the salient features of the action and regulation of MMPs