Monocyte and granulocyte-mediated tumor cell destruction. A role for the hydrogen peroxide-myeloperoxidase-chloride system

Abstract

Human monocytes stimulated with phorbol myristate acetate were able to destroy a T lymphoblast cell target (CEM). Stimulated human granulocytes were also capable of mediating CEM cytotoxicity to a comparable degree as the monocyte. CEM destruction was dependent on the pH and the effector cell number. Both monocyte or granulocyte mediated cytotoxicity were inhibited by the addition of catalase, whereas superoxide dismutase had no inhibitory effect. In addition, CEM were protected from cytolysis by the effector cells by the myeloperoxidase inhibitors, azide and cyanide, or by performing the experiment under halide-free conditions. Glucose oxidase, an enzyme system capable of generating hydrogen peroxide, did not mediate CEM cytotoxicity, while the addition of purified myeloperoxidase dramatically enhanced cytolysis. Hypochlorous acid scavengers prevented CEM destruction by the glucose oxidase-myeloperoxidase-chloride system but neither hydroxyl radical nor singlet oxygen scavengers had any protective effect. These hypochlorous acid scavengers were also successful in inhibiting monocyte or granulocyte-mediated CEM cytotoxicity. Based on these observations we propose that human monocytes or granulocytes can utilize the hydrogen peroxide-myeloperoxidase-chloride system to generate hypochlorous acid or species of similar reactivity as a potential mediator of CEM destruction.