LEUKOCYTE METABOLISM RELATED TO RECURRENT INFECTION

与反复感染相关的白细胞代谢

• 批准号: 3135876
• 负责人: ROBERT L BAEHNER
• 金额: $ 21.37万
• 依托单位: CHILDREN'S HOSPITAL OF LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-01-01 至 1987-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3135876
• 关键词: bactericidal immunity; chemical structure function; child (0-11); chronic granulomatous disease; glucose 6 phosphate dehydrogenase deficiency; human tissue; leukocyte disorder; leukocytes; lymphocytic leukemia; macrophage; myeloperoxidase; oxides; peroxidation; phagocytic dysfunction; phagocytosis; phosphoglycerate kinase deficiency; surface property

Polymorphonuclear leukocytes (PMN) and monocytes reduce oxygen during phagocytosis and elaborate a battery of oxidants (O2, H2O2, and 1O2) capable of inflicting damage to microbes and to surrounding tissues. Phagocytic cells may sustain autooxidative damage resulting in selective alterations of membrane-related and microtubule-related functions; membrane related include adherence, chemotaxis, recognition of opsonized particles and their ingestion; whereas, microtubule related functions include directed cell movement, distribution of lectin receptors in the cell surface, degranulation, and secretion of granular contents of the cell. This project will focus on the biochemical, cytoskeletal, and functional consequences of excessives and deficiencies of oxidation and oxygenation reactions in human and animal PMN and monocytes. The major objectives of this proposal are to locate the site of preferred substrate of the oxidase(s) responsible for the production of oxidants in mature and developing phagocytes, to define the natural antioxidants and their biochemical mechanisms which protect cytoskeletal components of the cell, to detail the alterations of membrane adherence, fluidity, receptor activity, microfilamatous gelation and contraction reactions in the phagocyte lacking Vitamin E, to determine the influence of prostaglandins and prostacyclins, especially PGE2 and PGI2 on membrane and cytoplasmic-associated phagocytic function, to investigate the pathologic consequences of iron overload, dietary excessives of polyunsaturates phagocytic function and to more precisely define the cellular basis for our observed beneficial effects of the oxidant drugs, ascorbic acid and dapsone, in the Chediak-Higashi syndrome and chronic granulomatous disease respectively.

中性粒细胞(PMN)和单核细胞在 吞噬和精心设计一组氧化剂(O2、H2O2和1O2)能够 对微生物和周围组织造成损害。吞噬细胞 可能会持续自氧化损伤，导致选择性改变 膜相关和微管相关功能；膜相关功能包括 黏附、趋化、识别调理颗粒及其摄取； 然而，与微管相关的功能包括定向细胞运动， 凝集素受体在细胞表面的分布、脱颗粒和 分泌细胞的颗粒状内容物。该项目将重点放在 过量和过量的生化、细胞骨架和功能后果 人和动物中性粒细胞氧化和氧合反应的缺陷及 单核细胞。这项提案的主要目标是确定 负责生产的氧化物酶的首选底物(S) 成熟和发育中的吞噬细胞中的氧化剂，以定义天然抗氧化剂 以及它们保护细胞骨架成分的生化机制 细胞，以详细说明膜黏附、流动性、受体的变化 吞噬细胞的活性、微丝凝胶化和收缩反应 缺乏维生素E，以确定前列腺素和 前列环素，特别是PGE2和PGI2在膜和细胞质上的相关 吞噬功能，以研究铁的病理后果 超负荷，饮食过量的多不饱和吞噬功能和更多 准确定义我们观察到的 Chediak-Higashi综合征患者的抗氧化剂、抗坏血酸和氨苯砜 慢性肉芽肿性疾病。