In vitro suppression of serum elastase-inhibitory capacity by reactive oxygen species generated by phagocytosing polymorphonuclear leukocytes.
Human polymorphonuclear leukocytes (PMN) phagocytosing opsonized antigen-antibody complexes, produce dialyzable species of activated oxygen which are capable of partially suppressing the elastase-inhibiting capacity (EIC) of whole human serum or purified human alpha1-proteinase inhibitor. Serum EIC was partially protially protected by superoxide dismutase, catalase, or mannitol, suggesting that hydroxyl radical, formed by interaction of superoxide radical and hydrogen peroxide, might be responsible for this effect. NaN3 also partly protected EIC, implicating myeloperoxidase-mediated reactions as well. An artificial superoxide rradical-generating system, involving xanthine and xanthine-oxidase, could be substituted for phagocytosing PMN with resultant EIC suppression. These results are consistent with previous demonstrations of the release of potent oxidants by stimulated PMN, as well as earlier studies from our laboratory showing sensitivity of alpha1-proteinase inhibitor to inactivation by oxidants. Oxidative inactivation of proteinase inhibitors in the microenvironment of PMN accumulating at sites of inflammation may allow proteases released from these cells to more readily damage adjacent connective tissue structures.
D002374:Catalase / Q000494:pharmacology; D006801:Humans; D008353:Mannitol / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010100:Oxygen; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D010587:Phagocytosis; D011480:Protease Inhibitors / Q000097:blood*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides; D014969:Xanthine Oxidase / Q000378:metabolism; D014970:Xanthines / Q000494:pharmacology
D011480:Protease Inhibitors; D014970:Xanthines; D013481:Superoxides; D008353:Mannitol; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D010196:Pancreatic Elastase; D010100:Oxygen