Oxidative regulation of neutrophil elastase-alpha-1-proteinase inhibitor interactions.
Triggered human neutrophils were able to maintain released elastase in an active form in the presence of purified alpha-1-proteinase inhibitor (alpha-1-PI), serum or bronchoalveolar lavage fluid (BAL). The accumulation of free elastase activity was associated with a decrease in the ability of the alpha-1-PI to inhibit porcine pancreatic elastase, an increase in proteinase activity associated with alpha-2-macroglobulin, and the oxidation of alpha-1-PI to a molecule containing four methionine sulfoxide residues. Neutrophils used both hypochlorous acid and long-lived N-chloroamines to oxidize the alpha-1-PI, but hypochlorous acid was preferentially used for suppressing the activity of the antiproteinase over short distances whereas the N-chloroamines were effective even when the phagocytes and alpha-1-PI were physically separated. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of purified alpha-1-PI, serum, or BAL that had been incubated with triggered neutrophils revealed that the released neutrophil elastase was not complexed with the antiproteinase and that a portion of the alpha-1-PI had undergone proteolysis. These data suggest that the presence of free neutrophil elastase as well as inactive, oxidized, and proteolyzed alpha-1-PI in fluids recovered from inflammatory sites in vivo could be directly mediated by triggered neutrophils alone.
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006801:Humans; D007163:Immunosorbent Techniques; D007700:Kinetics; D009504:Neutrophils / Q000201:enzymology*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D010196:Pancreatic Elastase / Q000097:blood*; D013482:Superoxide Dismutase / Q000378:metabolism; D013552:Swine; D000515:alpha 1-Antitrypsin
D000596:Amino Acids; D001798:Blood Proteins; D000515:alpha 1-Antitrypsin; D002374:Catalase; D013482:Superoxide Dismutase; D010196:Pancreatic Elastase; D003676:Deferoxamine; D010100:Oxygen; D004121:Dimethyl Sulfoxide