title: Human neutrophil elastase does not bind to alpha 1-protease inhibitor that has been exposed to activated human neutrophils.
abstract: The effect of leukocyte-derived oxidants on the elastase-inhibitory capacity of alpha 1-protease inhibitor was examined in an in vitro system using cells and purified proteins from human sources. The exposure of alpha 1-protease inhibitor to the myeloperoxidase-hydrogen peroxide-halide system resulted in a nearly complete loss of its ability to bind and inactivate purified human neutrophil elastase. A similar loss of binding to and inactivation of human neutrophil elastase was observed on exposure of alpha 1-protease inhibitor to human neutrophils in the presence of a halide and the neutrophil-activating agent, phorbol myristate acetate. This loss of elastase binding activity was abrogated by the addition of azide or catalase but not superoxide dismutase or heated catalase. The data suggest oxidative inactivation of alpha 1-protease inhibitor by secreted myeloperoxidase and hydrogen peroxide. Thus, the reported effects of leukocyte oxidants, especially the myeloperoxidase system, on alpha 1-protease inhibitor have been confirmed using the most pathophysiologically relevant protease, human neutrophil elastase, as the test enzyme. The role of the neutrophil in the pathogenesis of emphysema may, therefore, include the secretion of both elastase and oxidants that impair antielastase defenses.
mesh_terms: D001798:Blood Proteins / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D009504:Neutrophils / Q000201:enzymology*; D010084:Oxidation-Reduction; D010196:Pancreatic Elastase / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism / Q000494:pharmacology*; D010544:Peroxidases / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000378:metabolism*; D000515:alpha 1-Antitrypsin
chemical_list: D001798:Blood Proteins; D011480:Protease Inhibitors; D000515:alpha 1-Antitrypsin; D010544:Peroxidases; D009195:Peroxidase; D010196:Pancreatic Elastase