ETHANOL SUPPRESSION OF IMMUNE RESPONSE

乙醇抑制免疫反应

• 批准号: 3110806
• 负责人: RODNEY C. BAKER
• 金额: $ 11.56万
• 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/3110806
• 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.

过量饮酒与与之相关的疾病 长期酗酒会增加患酒精中毒的风险。 感染。有几个因素可能是导致增长的原因 酒精中毒患者感染的发生率和严重程度，例如； 机械防御能力受损，接触传染性疾病的机会增加 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 对防御系统的一个组件进行乙醇处理将是 调查过了。具体地说，该提案将解决 酒精处理对血小板功能和合成的影响 激活因子(PAF)与激活两个吞噬细胞有关 细胞类型：中性粒细胞和巨噬细胞。这两种单元格类型在中都起作用 一种吞噬和分泌能力来影响 增强和消退炎症。此外， 炎症细胞产生纤溶酶原激活物及纤溶酶原激活剂的作用 这些细胞提示PAF可能是一种重要的介导物， 或者是吞噬过程所必需的。 体外和慢性乙醇治疗对PAF的影响 调解的答复将在以下方面得到解决：1.招聘 细胞(趋化性)，2.吞噬外来颗粒，3. 脱颗粒，或分泌颗粒的释放。的影响 乙醇对PAF合成和降解的影响 对于磷脂酶A2、乙酰转移酶和 乙酰水解酶。目前的证据表明，PAF的产量 花生四烯酸代谢可能受到协调调节 从一种常见的前体1-0-烷基-2-花生四烯-锡-甘油-3- 由磷脂酶A2激活而启动的磷胆碱。 该反应的产物1-0-烷基-2-Lyso-GPC可以通过 酰化生成烷基磷脂酰胆碱，或酰化为 生产PAF。需要检验的假设是， PAF的产生及乙醇对其代谢的影响 PAF由以下因素决定：1.特定磷脂酶的活性 A2.2.乙酰转移酶或酰基转移酶的活性水平 走向1-0-烷基-2-赖索-GPC。3.酰基辅酶A或 乙酰辅酶A。4.分解代谢酶的活性； 乙酸水解酶。