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 H₂O₂ production are not cytotoxic, but activity is restored 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 reaction with a halide cofactor to damage the target cells.