MYELOPEROXIDASE AND LEUKOCYTE GRANULE COMPONENTS

髓过氧化物酶(MPO)、过氧化氢(H_2O_2)和氯离子(Cl-) 在中性粒细胞吞噬溶酶体内形成抗菌系统。在……里面 使用纯化的MPO进行的研究发现，抗菌活性 受某些含氮化合物(含氮化合物)调节的。在对…的研究中 刺激中性粒细胞，这些N-化合物影响中性粒细胞的比率 自我失活。这些效应的基础是MPO催化的氧化。 转化为次氯酸(HOC1)，它与N-化合物反应生成 含不同抗菌剂的氮氯(N-C1)衍生物 细胞毒活性。拟议的研究将考察 分离的中性粒细胞含有某些自然产生的N-化合物，这些化合物可能 在体内调节和调节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HOC1反应的是氨(NH4)、牛磺酸和蛋白质 从细胞质颗粒中分泌出来。HOCl2与环氧氯丙烷的反应 NH_4产生一氯胺(NH_2Cl)，这是一种亲脂性氧化剂，具有 具有很强的抗菌和细胞毒活性。NH_2C_1在细胞周期中的作用 中性粒细胞氧化毒性将用红细胞和 以细菌为靶细胞。HOC1与牛磺酸产率的反应 牛磺酸-一氯胺(TauNHCl)，一种亲水性氧化剂 或者没有毒性。TauNHCl及其相关N-C_1的形成和毒性 将在可能增加毒性的条件下研究衍生品： (A)当tauNHC1通过膜转运到靶细胞时 运输系统，以及(B)当tauNHC1与NH4反应生成NH2Cl时。 依赖NH4的毒性将用细菌、红细胞和 以肿瘤细胞为靶点。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。HOCl2的反应 与组胺产生组胺-一氯胺(HisNHC1)，它具有 亲水性或亲油性的不同寻常的性质，取决于 PH值。受刺激的中性粒细胞对组胺的氯化作用 HisNHC1，以及hisNHC1对中性粒细胞功能的影响。 其目的是加深对中性粒细胞调节的理解。 氧化毒性，从而导致新的方法增加 在保护正常组织免受氧化的同时抵抗感染 进攻。

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.