MYELOPEROXIDASE AND LEUKOCYTE GRANULE COMPONENTS

髓过氧化物酶（MPO）、过氧化氢（H2 O2）和氯离子（C1-） 在嗜中性粒细胞的吞噬溶酶体内形成抗菌系统。 在 使用纯化的MPO进行的研究发现， 由某些含氮化合物（N-化合物）调节。 研究的 刺激中性粒细胞，这些N-化合物影响中性粒细胞的速率 自我失活 这些效应的基础是MPO催化氧化 C1-次氯酸（HOC 1），它与N-化合物反应， 氮-氯（N-C1）衍生物，具有不同的抗微生物和 细胞毒活性。 拟议的研究将审查以下方面的相互作用： 分离的中性粒细胞与某些天然存在的N-化合物， 介导和调节体内嗜中性粒细胞的氧化毒性。 当在体外研究刺激的中性粒细胞时，主要的N-化合物 可与HOC 1反应的是氨（NH 4+）、牛磺酸和蛋白质 从细胞质颗粒中分泌出来。 HOC 1与 NH 4+产生一氯胺（NH 2Cl），一种亲脂性氧化剂， 有效的抗微生物和细胞毒性活性。 NH 2C 1的作用 将用红细胞研究中性粒细胞氧化毒性， 细菌作为靶细胞。 HOC 1与牛磺酸的反应产生 牛磺酸-一氯胺（tauNHCl），一种亲水性氧化剂， 或无毒性。 tauNHC 1和相关N-C1的形成和毒性 将在可能促进毒性的条件下研究衍生物： (a)当tauNHCl通过膜转运到靶细胞中时 （B）当tauNHCl与NH 4+反应产生NH 2Cl时。 NH 4+依赖性毒性将用细菌、红细胞和 肿瘤细胞作为靶点。 组胺是一种天然存在的N-化合物， 中性粒细胞在体内遇到高浓度。 HOC 1的反应 与组胺反应产生组胺-一氯胺（hisNHCl），其具有 亲水性或亲脂性的不寻常性质，取决于 博士 组胺被刺激的中性粒细胞氯化， hisNHC 1，以及hisNHC 1对中性粒细胞功能的影响将被研究。 目的是增加对中性粒细胞调节的了解， 氧化毒性，从而导致新的方法，以增加 抗感染，同时保护正常组织免受氧化 攻击

Myeloperoxidase (MPO), hydrogen peroxide (H2O2), and chloride ion (C1-) form an antimicrobial system within phagolysosomes of neutrophils. In studies using purified MPO, antimicrobial activity was found to be modulated by certain nitrogen compounds (N-compounds). In studies on stimulated neutrophils, these N-compounds influenced the rate of neutrophil self-inactivation. The basis of these effects is MPO-catalyzed oxidation of C1- to hypochlorous acid (HOC1), which reacts with N-compounds to yield nitrogen-chlorine (N-C1) derivatives with differing antimicrobial and cytotoxic activities. The proposed studies will examine the interaction of isolated neutrophils with certain naturally occurring N-compounds that may mediate and regulate the oxidative toxicity of neutrophils in vivo. When stimulated neutrophils are studied in vitro, the major N-compounds available for reaction with HOC1 are ammonia (NH4+), taurine, and proteins that are secreted from the cytoplasmic granules. The reaction of HOC1 with NH4+ yields monochloramine (NH2C1), a lipophilic oxidizing agent with potent antimicrobial and cytotoxic activity. The role of NH2C1 in neutrophil oxidative toxicity will be studied with erythrocytes and bacteria as target cells. The reaction of HOC1 with taurine yields taurine-monochloramine (tauNHC1), a hydrophilic oxidizing agent with little or no toxicity. Formation and toxicity of tauNHC1 and related N-C1 derivatives will be studied under conditions that may promote toxicity: (a) when tauNHC1 is transported into the target-cell by a membrane transport system, and (b) when tauNHC1 reacts with NH4+ to yield NH2C1. NH4+-dependent toxicity will be studied with bacteria, erythrocytes and tumor cells as targets. Histamine is a naturally occurring N-compound that neutrophils encounter in high concentrations in vivo. The reaction of HOC1 with histamine yields histamine-monochloramine (hisNHC1), which has the unusual property of being either hydrophilic or lipophilic, depending on pH. Chlorination of histamine by stimulated neutrophils, the fate of hisNHC1, and the effect of hisNHC1 on neutrophil functions will be studied. The goal is to gain increased understanding of the regulation of neutrophil oxidative toxicity, so as to lead to new approaches to increasing resistance to infection while protecting normal tissues against oxidative attack.