URINARY TRYPSIN-INHIBITOR PROTECTS NEUTROPHIL CHEMOTAXIS IN THE INFLAMMATORY RESPONSE

Abstract

The aim of this study was to assess the contribution of physiological protease inhibitors (urinary trypsin inhibitor [UTI] and alpha 1-antitrypsin [alpha 1AT]) to the inhibition of trypsin and human leukocyte elastase (HLE) activities, to examine whether UTI and UTI-trypsin complexes compete for binding of alpha 1AT-HLE complexes to human neutrophils and promyeloid leukemia U937 cells, and to determine whether the modified ligands for the serpin-enzyme complex (SEC) receptor have neutrophil chemotactic activity. UTI is a strong inhibitor for trypsin and HLE and is relatively resistant to inactivation by trypsin,while the decline in inhibitor activity of alpha 1AT proceeds faster by trypsin. UTI protects the inactivation of alpha 1AT by trypsin. The SEC receptor mediates neutrophil chemotactic activity of alpha 1AT-HLE complexes. UTI and UTI-trypsin complexes failed to bind to the SEC receptor on neutrophils, and they did not inhibit alpha 1AT-HLE complexes-mediated neutrophil chemotactic activity. When alpha 1AT treated with trypsin was incubated with HLE, neutrophil chemotactic activity was inhibited. In the presence of UTI, however, UTI protected neutrophil chemotaxis mediated through SEC receptor. The present study suggests another working hypothesis that, besides the effects on anti-protease activity, UTI plays an important role in inhibition of inactivation/degradation of alpha 1AT by trypsin and in protection of neutrophil chemotaxis.