TOXICOLOGICAL IMPORTANCE OF LIVER GLUTATHIONE

产品说明： （摘自《研究者摘要》） 本建议的目的是研究反应性的核心作用， 肝脏巨噬细胞和中性粒细胞释放的氧气 内毒素诱导的肝损伤的发病机制，并测试 假设谷胱甘肽（GSH）的释放增强， 肝细胞作为肝脏的内源性防御系统发挥作用， 活性氧物种。 建立内毒素模型- 诱导的肝损伤将被用来调查的时间 氧化应激、中性粒细胞定位与细胞凋亡的关系 肝脏和肝脏损伤。 细胞外和细胞内 活性氧的形成将在体内定量， 氧化型谷胱甘肽的测量，分离后， 巨噬细胞和嗜中性粒细胞从肝脏，细胞来源， 氧化应激的性质将被确定。 的改变 不同预处理条件下肝巨噬细胞的数量和启动状态 或阻断中性粒细胞粘附和功能， 开发了针对β 2-整合素的单克隆抗体， 中性粒细胞（CD 11/CD 18家族）和肝细胞上的ICAM将用于 探讨活性氧在发病机制中的作用。 的 GSH的保护作用将通过操纵 肝细胞谷胱甘肽含量和血浆GSH浓度。 嗜酸性粒细胞诱导的实质细胞损伤的机制， 特别是中性粒细胞上粘附分子的作用， 将使用流式细胞术在分离的细胞中研究肝细胞 和荧光成像技术。 这项研究的信息 将深入了解组织巨噬细胞和中性粒细胞的作用 在内毒素性肝损伤中的作用及其潜在的治疗价值 谷胱甘肽。

DESCRIPTION: (Adapted from the Investigator's Abstract) The major objective of this proposal is to study the central role of reactive oxygen released by liver macrophages and neutrophils in the pathogenesisof endotoxin-induced liver injury and to test the hypothesis that the enhancedrelease of glutathione (GSH) from hepatocytes functions asan endogenous defense system of the liver to scavenge reactive oxygen species. Established models of endotoxin- induced liver injury will be used to investigate the temporal relationship between the oxidant stress, neutrophil localization in the liver and liver injury in vivo. Extracellular and intracellular reactive oxygen formation will be quantified in vivo through measurements of oxidized glutathione and, after isolation of macrophages and neutrophils from the liver, the cellular source and the nature ofthe oxidant stress will be identified. Alterations of the number and priming status of liver macrophages with various pretreatments or blocking of neutrophil adhesion and functions through newly developed monoclonalantibodies directed against the beta2- integrins on neutrophils (CD11/CD18 family) and ICAM on hepatocytes will be used to investigate the role of reactive oxygen in the pathogenesis. The protective role of GSH will be tested by manipulation of the hepatocellular glutathione content and plasma GSH concentrations. The mechanism of neutrophil-induced parenchymal cell injury, particularly the role of adhesion molecules on neutrophils and hepatocytes will be studied in isolated cells using flow cytometric and fluorescence imaging techniques. Theinformation from this study will give insight into the role of tissue macrophages and neutrophils in endotoxin-induced liver injury and the potential therapeutic value of glutathione.