Phagocytosing Polymorphonuclear Leukocytes

A B S T R A C T 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 a1-proteinase inhibitor. Serum EIC was partially 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 radical-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 a1-proteinase inhibitor to inactivation by oxidants. Oxidative inactivation ofproteinase inhibitors in the microenvironment ofPMN accumulating at sites of inflammation may allow proteases released from these cells to more readily damage adjacent connective tissue structures.