INHIBITORY PROPERTIES OF RECOMBINANT HUMAN MONOCYTE NEUTROPHIL ELASTASE INHIBITOR

Human monocyte/neutrophil elastase inhibitor (HEI) is a serpin superfa mily protein that rapidly and irreversibly inhibits neutrophil and pan creatic elastase. We generated a recombinant baculovirus that supports production of HEI in insect cells at approximately 400 times the leve l in monocytes. Recombinant HEI was found to be indistinguishable from monocyte HEI in its physicochemical properties and ability to inhibit neutrophil elastase and pancreatic elastase, The recombinant protein was used to test for additional functions. HEI was shown to inhibit pr oteinase 3, an important neutrophil inflammatory protease, by the clas sical serpin mechanism of forming a covalent protease-protease inhibit or complex. Preliminary evidence suggests that HEI also inhibits neutr ophil cathepsin G. On the ether hand, HEI does not inhibit u-plasminog en activator (urokinase). These findings suggest that HEI functions as a class-specific regulator of the neutrophil serine proteases charact eristically found at inflammatory sites.