The role of superoxide in the destruction of erythrocyte targets by human neutrophils.
Human neutrophils exposed to the soluble stimulus, phorbol myristate acetate, generate a flux of O2.- which can destroy human erythrocyte targets. Under optimal conditions, each neutrophil was capable of lysing almost 10 erythrocyte targets. Hemolysis was inhibited by exogenous copper-zinc or iron superoxide dismutase while neither heat-denatured enzyme nor albumin inhibited cytotoxicity. Although neutrophils can also generate H2O2, neither catalase nor a glutathione-glutathione peroxidase system inhibited hemolysis. Hemolysis was prevented by conversion of the hemoglobin to carbon monoxyhemoglobin, suggesting an intracellular mechanism of cytotoxicity. Conversion of hemoglobin to methemoglobin by nitrite treatment did not impair neutrophil-mediated hemolysis. However, nitrite-treated targets were not protected by superoxide dismutase, while exogenous catalase inhibited cytotoxicity, suggesting a potential role for H2O2 and methemoglobin. H2O2 and methemoglobin are known to interact to form an oxidant complex whose cytotoxic potential was underlined by the marked sensitivity of nitrite-treated cells to commercial H2O2. It is proposed that neutrophil-derived O2.- oxidizes oxyhemoglobin to generate methemoglobin and H2O2 which interact to form a cytotoxic complex capable of hemolyzing the erythrocyte target.
D000818:Animals; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010100:Oxygen / Q000097:blood*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000097:blood*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology
D013481:Superoxides; D003300:Copper; D013482:Superoxide Dismutase; D015032:Zinc; D013755:Tetradecanoylphorbol Acetate; D010100:Oxygen