ANTIMICROBIAL EFFECT OF PEROXIDASE - ROLE IN LEUKOCYTES

我们建议对其性质、作用机制和生物学特性进行研究。 吞噬细胞的氧依赖抗菌系统的意义。 吞噬细胞对质膜的扰动有一种突发性反应 氧气消耗和额外消耗的氧气转化为超氧化物 阴离子、过氧化氢、羟基自由基和可能的单线态氧， 它们中的每一个都可能有助于细胞的杀菌活性。这个 过氧化物酶的加入大大增加了过氧化氢的毒性。 一种卤化物和这个抗菌系统似乎在 某些吞噬细胞(如中性粒细胞、单核细胞)。我们的目标是确定 这些抗菌系统破坏靶细胞的机制 重点是铁中心的氧化和铁的释放 变成了媒介。完整的生物体、膜泡或模型 含铁化合物将暴露在孤立的抗菌系统中 在某些情况下，对完整的吞噬细胞也是如此。生物体将会是 59Fe预标记，聚丙烯酰胺凝胶电泳法， 将使用放射自显影和组织化学染色来鉴定 蛋白质主要受影响。对被释放的铁的结合 由于存在这种铁结合蛋白，因此将对乳铁蛋白进行研究 在中性粒细胞颗粒中，并可作为铁的生物螯合剂 在原地。一种新型含铁抗菌体系的性能研究 由铁、过氧化氢和碘化物组成的研究将重点放在 该系统在生物水消毒中的应用 会导致腹泻(如贾第鞭毛虫包囊)。易感性的研究 麻风分枝杆菌胞内致病菌对抗菌药的影响 将进行吞噬细胞系统的研究，试图确定 它们的寄主抗性的基础。一种显微和代谢方法 将对麻风活性的快速检测进行评估。中性粒细胞 选定的易感性增加的患者的功能 将对感染进行评估，试图阐明感染的基础 功能障碍。长期目标是1)确定这些因素的作用 吞噬细胞杀灭微生物的系统；2)确定 这些系统的改变是否参与了糖尿病的发病 疾病；以及3)确定对这些系统的操纵 影响疾病的进程。

We propose to study the properties, mechanism of action and biological significance the oxygen-dependent antimicrobial systems of phagocytes. Phagocytes respond to perturbation of the plasma membrane with a burst of oxygen consumption and extra oxygen consumed is converted to the superoxide anion, hydrogen peroxide, hydroxyl radicals and possible singlet oxygen, each of which may contribute to themicrobicidal activity of the cells. the toxicity of H2O2 is increased considerably by the addition of peroxidase and a halide and this antimicrobial system appears to play a role in certain phagocytes (e.g. neutrophils, monocytes). Our aim is to determine the mechanism of target cell destruction by these antimicrobial systems with emphasis on the oxidation of iron centers with the release of iron into the medium. Intact organisms, membrane vesicles or model iron-containing compounds will be exposed to isolated antimicrobial systems and, in some instances, to intact phagocytes. The organisms will be prelabeled with 59Fe, and polyacrylamide gel electrophoresis, radioautography and histochemical staining will be employed to identify the proteins primarily affected. The binding of the released iron by lactoferrin will be investigated since this iron-binding protein is present in neutrophil granules and may serve as a biological chelator of the iron in situ. The properties of a new iron-containing antimicrobial system consisting of iron, H2O2 and iodide will be investigated with emphasis on the usefulness of this system for the disinfection of water of organisms which induce diarrhea (e.g. Giardia cysts). A study of the susceptibility of the intracellular pathogen Mycobacterium leprae to the antimicrobial systems of phagocytes will be undertaken in an attempt to determine the basis for their host resistance. A microscopic and metabolic method for the rapid detection of viability of M leprae will be evaluated. Neutrophil function of selected patients with an increased susceptibility to infectionwill be evaluated in an attempt to elucidate the basis for the dysfunction. The long term goals are 1) to determine the role of these systems in the killing of microorganisms by phagocytes; 2) to determine whether alterations in these systems contribute to the pathogenesis of disease; and 3) to determine whether manipulations of these systems influence the course of disease.