Weiss S J, Klein R, Slivka A, Wei M
J Clin Invest. 1982 Sep;70(3):598-607. doi: 10.1172/jci110652.
The model hydrogen peroxide-myeloperoxidase-chloride system is capable of generating the powerful oxidant hypochlorous acid, which can be quantitated by trapping the generated species with the beta-amino acid, taurine. The resultant stable product, taurine chloramine, can be quantitated by its ability to oxidize the sulfhydryl compound, 5-thio-2-nitro-benzoic acid to the disulfide, 5,5'-dithiobis(2-nitroben-zoic acid) or to oxidize iodide to iodine. Using this system, purified myeloperoxidase in the presence of chloride and taurine converted stoichiometric quantities of hydrogen peroxide to taurine chloramine. Chloramine generation was absolutely dependent on hydrogen peroxide, myeloperoxidase, and chloride and could be inhibited by catalase, myeloperoxidase inhibitors, or chloride-free conditions. In the presence of taurine, intact human neutrophils stimulated with either phorbol myristate acetate or opsonized zymosan particles generated a stable species capable of oxidizing 5-thio-2-nitrobenzoic acid or iodide. Resting cells did not form this species. The oxidant formed by the stimulated neutrophils was identified as taurine chloramine by both ultraviolet spectrophotometry and electrophoresis. Taurine chloramine formation by the neutrophil was dependent on the taurine concentration, time, and cell number. Neutrophil-dependent chloramine generation was inhibited by catalase, the myeloperoxidase inhibitors, azide, cyanide, or aminotriazole and by chloride-free conditions, but not by superoxide dismutase or hydroxyl radical scavengers. Thus, it appears that stimulated human neutrophils can utilize the hydrogen peroxide-myeloperoxidase-chloride system to generate taurine chloramine. Based on the demonstrated ability of the myeloperoxidase system to generate free hypochlorous acid we conclude that neutrophils chlorinate taurine by producing this powerful oxidant. The biologic reactivity and cytotoxic potential of hypochlorous acid and its chloramine derivatives suggest that these oxidants play an important role in the inflammatory response and host defense.
典型的过氧化氢-髓过氧化物酶-氯化物系统能够生成强氧化剂次氯酸，次氯酸可通过用β-氨基酸牛磺酸捕获生成的物质来进行定量。生成的稳定产物牛磺酰胺氯可通过其将巯基化合物5-硫代-2-硝基苯甲酸氧化为二硫化物5,5'-二硫代双(2-硝基苯甲酸)或氧化碘离子为碘的能力来定量。利用该系统，在氯化物和牛磺酸存在的情况下，纯化的髓过氧化物酶能将化学计量的过氧化氢转化为牛磺酰胺氯。氯胺的生成绝对依赖于过氧化氢、髓过氧化物酶和氯化物，并且可被过氧化氢酶、髓过氧化物酶抑制剂或无氯化物条件所抑制。在牛磺酸存在的情况下，用佛波酯肉豆蔻酸乙酸酯或调理酵母聚糖颗粒刺激完整的人中性粒细胞会生成一种能够氧化5-硫代-2-硝基苯甲酸或碘离子的稳定物质。静息细胞不会形成这种物质。通过紫外分光光度法和电泳鉴定，受刺激的中性粒细胞形成的氧化剂为牛磺酰胺氯。中性粒细胞生成牛磺酰胺氯取决于牛磺酸浓度、时间和细胞数量。中性粒细胞依赖性氯胺生成受到过氧化氢酶、髓过氧化物酶抑制剂、叠氮化物、氰化物或氨基三唑以及无氯化物条件的抑制，但不受超氧化物歧化酶或羟基自由基清除剂的抑制。因此，似乎受刺激的人中性粒细胞可以利用过氧化氢-髓过氧化物酶-氯化物系统生成牛磺酰胺氯。基于髓过氧化物酶系统生成游离次氯酸的已证实能力，我们得出结论，中性粒细胞通过产生这种强氧化剂使牛磺酸氯化。次氯酸及其氯胺衍生物的生物反应性和细胞毒性潜力表明，这些氧化剂在炎症反应和宿主防御中起重要作用。
