WHITE BLOOD CELL OXIDASE--NORMAL AND ABNORMAL

白细胞氧化酶——正常和异常

• 批准号: 3129008
• 负责人: HARVEY J COHEN
• 金额: $ 19.93万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-01-01 至 1992-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3129008
• 关键词: acidity /alkalinity; arachidonate; calcium; calmodulin; cell biology; cellular respiration; cytoplasm; enzyme mechanism; fluorescent dye /probe; granulocyte; guanosine triphosphate; human tissue; immunohematology; laboratory mouse; leukocyte activation /transformation; macrophage; membrane potentials; membrane structure; molecular biology; monoclonal antibody; monocyte; oxidoreductase; phagocytosis; phorbols; phosphatase inhibitor; phosphatidylinositols; phosphorylation; protease inhibitor; protein kinase C; radiotracer; superoxides; tissue /cell culture

Phagocytic cells undergo both metabolic and structural changes when stimulated with either soluble or particulate stimuli. These changes, either spontaneously terminate after a short period of time, or can be made to cease with removal of the stimuli. The overall goal of the proposed investigations for the next five years are to gain a better understanding of the cellular and biochemical aspects, of both reversible and irreversible inactivation of the oxidase system responsible for killing bacteria, and for some of the destructive ability of phagocytic cells. We plan to determine the kinetics of inactivation of both the whole cell superoxide generating system and the particulate fraction - NADPH oxidase - in both the reversible and irreversible manner, and in the presence of various manipulations. These studies will be performed in granulocytes, moncytes and monocyte-derived macrophages. We plan to determine the cellular events that accompany both reversible and irreversible inactivations concentrating on changes in intracellular calcium, membrane potential an intracellular pH together with phosphatidyl inositol metabolism and protein phosphorylation. Finally, we plan to determine the molecular and biochemical events associated with inactivation of the oxidase activated in subcellular particles, the PMA stimulated protein kinase C dependent activity, and the arachidonic acid stimulated soluble factor dependent activity. In these studies we plan to determine the effects of protein kinase C, calmodulin modifiers, and GTP analogs on the inactivation process. By examining cellular and subcellular aspects of inactivation, we hope to gain a better understanding of the control of this important process.

当吞噬细胞发生代谢和结构变化时 用可溶性或颗粒刺激刺激。 这些 变化，要么在短时间后自发终止 时间，或者可以通过去除刺激而停止。 这 未来五年拟议调查的总体目标 为了更好地了解细胞和生化 可逆性和不可逆转的灭活方面 负责杀死细菌的氧化酶系统，其中一些 吞噬细胞的破坏性能力。 我们计划确定 整个细胞超氧化物的失活动力学 生成系统和颗粒分数-NADPH氧化酶 - 以可逆和不可逆的方式以及在场 各种操纵。 这些研究将在 粒细胞，主张和单核细胞衍生的巨噬细胞。 我们计划 确定伴随可逆的细胞事件和 不可逆转的失活集中于变化 细胞内钙，膜电势一个细胞内pH 与磷脂酰肌醇代谢和蛋白质一起 磷酸化。 最后，我们计划确定分子和 与氧化酶失活有关的生化事件 在亚细胞颗粒中激活，PMA刺激蛋白 激酶C依赖性活性，而花生四烯酸刺激了 可溶性因子依赖性活性。 在这些研究中，我们计划 确定蛋白激酶C，钙调蛋白修饰剂的影响， 和GTP类似物在灭活过程中。 通过检查细胞 和灭活的亚细胞方面，我们希望能获得更好的 了解对这个重要过程的控制。