HUMAN NEUTROPHILS EMPLOY CHLORINE GAS AS AN OXIDANT DURING PHAGOCYTOSIS

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Reactive oxidants generated by phagocytes are of central importance in host defenses, tumor surveillance, and inflammation. One important pathway involves the generation of potent halogenating agents by the myeloperoxidase-hydrogen peroxide-chloride system. The chlorinating intermediate in these reactions is generally believed to be HOC1 or its conjugate base, CIO-. However, HOC1 is also in equilibrium with C12, raising the possibility that C12 executes oxidation/halogenation reactions that have previously been attributed to HOC1/CIO-. In this study gas chromatography-mass spectrometric analysis of head space gas revealed that the complete myeloperoxidase-hydrogen peroxide-chloride system generated C12. In vitro studies demonstrated that chlorination of the aromatic ring of free L-tyrosine was mediated by C12 and not by HOC1/CIO- Collectively, these results demonstrate that myeloperoxidase generates C12 and that human neutrophils use an oxidant with characteristics ide ntical to those of C12 during phagocytosis. Moreover, our observations suggest that phagocytes exploit the chlorinating properties of C12 to execute oxidative and cytotoxic reactions at sites of inflammation and vascular disease.