ETHANOL SUPPRESSION OF IMMUNE RESPONSE

乙醇抑制免疫反应

• 批准号: 3110805
• 负责人: RODNEY C. BAKER
• 金额: $ 10.49万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1990-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3110805
• 关键词: acetyl coA; acyl coA; alcoholic beverage consumption; alcoholism /alcohol abuse; centrifugation; chemotaxis; clone cells; enzyme mechanism; ethanol; gas chromatography; high performance liquid chromatography; inflammation; interleukin 1; laboratory mouse; macrophage; neutrophil; phagocytosis; platelet activating factor; proteolysis; secretion; spectrometry; thin layer chromatography; transferase

Excessive alcohol consumption and the diseases associated with long term alcohol abuse are linked with an increased risk of infection. Several factors may contribute to the increased incidence and severity of infections in alcoholic patients, such as; impaired mechanical defense, increased exposure to infectious agents, nutritional status of the patient and disorders of the host defense system. In this proposal, the effect of chronic and acute ethanol treatment on a component of the defense system will be investigated. Specifically, the proposal will address the effect of alcohol treatment on the function and synthesis of platelet activating factor (PAF) in regards to activation of two phagocytic cell types; neutrophil and macrophage. Both cell types function in a phagocytic and secretory capacity to influence both the potentiation and resolution of inflammation. In addition, the production of PAF by inflammatory cells and actions of PAF on these cells suggests that PAF may be an important mediator of, or be required for, the phagocytic process. The effect of in vitro and chronic ethanol treatment of PAF mediated responses will be addressed in regard to; 1. recruitment of cells (chemotaxis), 2. phagocytosis of foreign particles and 3. degranulation, or release of secretory granules. The effect of ethanol on the synthesis and degradation of PAF will be directed toward enzymes phospholipase A2, acetyltransferase and acetylhydrolase. Current evidence suggests that PAF production and arachidonic acid metabolism may be coordinately regulated from a common precursor, 1-0-alkyl-2-arachidonly-sn-glycerol-3- phosphocholine, initiated by the activation of phospholipase A2. The product of this reaction, 1-0-alkyl-2-lyso-GPC can by acylated to form alkylphosphatidylcholine, or actylated to produce PAF. The hypothesis to be tested is that the amount of PAF produced and the effect of ethanol on the metabolism of PAF is determined by: 1. The activity of a specific phospholipase A2. 2. The level of acetyltransferase or acyltransferase activity toward 1-0-alkyl-2-lyso-GPC. 3. The availability of acyl CoA or acetyl CoA. 4. The activity of the catabolic enzyme, acethydrolase.

过度饮酒和与之相关的疾病 长期酗酒会增加 感染 有几个因素可能导致 酗酒患者感染的发生率和严重程度，例如; 受损的机械防御，增加接触传染性 病原体、患者的营养状况和宿主的疾病 防御系统 在这项建议中，慢性和急性的影响， 乙醇处理的一个组成部分的防御系统将是 研究了 具体而言，该提案将解决以下影响： 酒精对血小板功能和合成的影响 活化因子（PAF）在活化两种吞噬细胞 细胞类型;嗜中性粒细胞和巨噬细胞。 这两种细胞类型的功能， 吞噬和分泌的能力，以影响 增强和消除炎症。 此外该 炎症细胞产生血小板活化因子及血小板活化因子的作用 这些细胞表明PAF可能是一种重要的介导因子， 或者是吞噬过程所必需的。 体外及慢性乙醇处理对血小板活化因子的影响 调解的反应将涉及; 1.招聘 细胞的趋化性（chemotaxis），2。吞噬外来颗粒和3. 脱粒或分泌颗粒的释放。 的影响 乙醇对PAF合成和降解的影响 磷脂酶A2、乙酰转移酶和 乙酰水解酶 目前的证据表明，PAF生产 和花生四烯酸代谢可能是协同调节的 从常见的前体1-O-烷基-2-花生四烯基-Sn-甘油-3- 磷酸胆碱，由磷脂酶A2的活化引发。 该反应的产物1-0-烷基-2-溶血-GPC可以通过 酰化以形成烷基磷脂酰胆碱，或酰化以 生产PAF。 要检验的假设是， PAF的产生及乙醇对PAF代谢的影响 PAF由以下公式确定：1。一种特定磷脂酶的活性 A2. 2.乙酰转移酶或酰基转移酶活性水平 向1-O-烷基-2-溶血-GPC转化。 3.酰基辅酶A或 乙酰辅酶A 4.分解代谢酶的活性， 乙酰水解酶。