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.