Myeloperoxidase--H2O2--halide system: cytotoxic effect on human blood leukocytes

Abstract

Myeloperoxidase, H2O2, and a halide form a potent antimicrobial and cytotoxic system of the polymorphonuclear leukocyte. A cytotoxic effect of this system on human blood leukocytes is demonstrated, employing 51Cr release and dye exclusion assays. Cytotoxicity is dependent on enzymatically active myeloperoxidase, H2O2, or a peroxide-generating enzyme system and either chloride or iodide. Cell damage is rapid, with maximal levels of 51Cr release occurring within 30--60 min. Approximately equal sensitivity to the peroxidase system is observed for polymorphonuclear leukocytes and mononuclear leukocytes. Since myeloperoxidase and H2O2 are released from polymorphonuclear leukocytes under certain conditions, such as during particle ingestion, it is suggested that peroxidase-mediated leukocyte injury may be an important feature of the inflammatory response.