Neutrophil-mediated tumor cell cytotoxicity: role of the peroxidase system.
A cytotoxic effect of human neutrophils on mammalian tumor cells is demonstrated. Cytotoxicity depends on the presence of intact neutrophils, phagocytosable particles, and a halide cofactor and is inhibited by azide, cyanide, and catalase. Neutrophils from patients with myeloperoxidase (MPO) deficiency or defective H1O2 production are not cytotoxic, but activity is resotred by addition of purified MPO or H2O2 respectively. The findings support a mechanism involving the phagocytosis-induced extracellular release of MPO and H2O2 and their reation with a halide cofactor to damage the target cells.
D000818:Animals; D001386:Azides / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism; D002860:Chromium Radioisotopes; D003486:Cyanides / Q000494:pharmacology; D003601:Cytotoxicity Tests, Immunologic; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000276:immunology; D006105:Granulomatous Disease, Chronic / Q000276:immunology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007454:Iodides / Q000378:metabolism; D008223:Lymphoma / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology*; D009895:Opsonin Proteins; D009195:Peroxidase / Q000172:deficiency / Q000378:metabolism*; D010544:Peroxidases / Q000378:metabolism*; D010587:Phagocytosis; D015054:Zymosan / Q000494:pharmacology
D001386:Azides; D002712:Chlorides; D002860:Chromium Radioisotopes; D003486:Cyanides; D007454:Iodides; D009895:Opsonin Proteins; D015054:Zymosan; D006861:Hydrogen Peroxide; D010544:Peroxidases; D002374:Catalase; D009195:Peroxidase