MATRILYSIN IS MUCH MORE EFFICIENT THAN OTHER MATRIX METALLOPROTEINASES IN THE PROTEOLYTIC INACTIVATION OF ALPHA(1)-ANTITRYPSIN

alpha(1)-antitrypsin, the primary physiologic inhibitor of human leuko cyte elastase, is proteolytically inactivated by several matrix metall oproteinases including interstitial collagenase, stromelysin and 92 kD a gelatinase. In this report, we describe the catalytic effects of mat rilysin, a recently identified metalloproteinase, upon alpha(1)-antitr ypsin. Matrilysin was found to be approximately 30-fold more effective than 92 kDa gelatinase, 70-fold more effective than collagenase, and 180-fold more effective than stromelysin. Cleavage of alpha(1)-antitry psin by matrilysin produced two fragments of approximately 50 kDa and 4 kDa. The single cleavage occurred at the Phe(352).Leu(353) peptide b ond, a locus within alpha(1)-antitrypsin's active-site loop. These res ults suggest that apart from its activity against extracellular matrix , matrilysin provides a mechanism for the regulation of leukocyte elas tase activity through its capacity to degrade alpha(1)-AT. (C) 1994 Ac ademic Press, Inc.