HUMAN NEUTROPHILS EMPLOY CHLORINE GAS AS AN OXIDANT DURING PHAGOCYTOSIS

吞噬细胞产生的活性氧化剂是 在宿主防御、肿瘤监测和炎症方面的重要性。 一条重要的途径是产生有效的卤化作用。 髓过氧化物酶-过氧化氢-氯化物体系的试剂。这个 这些反应中的氯化中间体通常被认为是 为HOC1或其共轭碱基，CIO-。然而，HOC1也在 与C12的平衡，增加了C12执行的可能性 以前被认为是氧化/卤化反应 致HOC1/CIO-。在这项研究中，气相色谱-质谱仪 顶空气体的分析显示，完整的 髓过氧化物酶-过氧化氢-氯化物体系产生C12。在……里面 体外研究表明，芳香环的氯化 游离的L酪氨酸是由C12介导的，而不是由HOC1/Cio共同介导的。 这些结果表明髓过氧化物酶产生C12，并且 人类中性粒细胞使用一种氧化剂，其特性与 吞噬过程中C12的表达。此外，我们的观察表明 吞噬细胞利用C12的氯化特性来执行 炎症和炎症部位的氧化和细胞毒性反应 血管疾病。

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.