ETHANOL SUPPRESSION OF IMMUNA RESPONSE

乙醇抑制免疫反应

• 批准号: 3110808
• 负责人: RODNEY C. BAKER
• 金额: $ 12.99万
• 依托单位: UNIVERSITY OF MISSISSIPPI MED CTR
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-07-01 至 1996-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3110808
• 关键词: B lymphocyte; T lymphocyte; acyltransferase; antigen presentation; arachidonate; cellular immunity; eicosanoid metabolism; enzyme activity; ethanol; high performance liquid chromatography; laboratory mouse; lipid biosynthesis; lipid metabolism; macrophage; membrane activity; membrane lipids; phospholipase A2; phospholipase D; phospholipids; phosphotransferases; platelet activating factor; thin layer chromatography; tissue /cell culture; toxicology; transferase

This proposal addresses the effect of ethanol on lymphocyte and leukocyte membrane phospholipid metabolism as a component of the aberrant immune response associated with chronic ethanol treatment. Basic to the proposal is the consideration that specific membrane phospholipids are necessary for an "optimal" immune response. The necessary membrane phospholipids or their may either be present in immune cell membranes or be produced as a response to stimuli. We propose that ethanol alters immune function, in part, by altering a number of phospholipid associated enzyme activities including; acyltransferase, acetyltransferase, cholinephosphate cytidyltransferase, cholinephosphotransferase, phospholipase A2 and phospholipase D. The consequences of influencing these enzymatic activities may be to produce an abnormal array of lipid mediators or activators associated with lymphocyte and leukocyte function and thus alter their capacity to express cell surface antigens, to transport ions, secret proteins and thus impair communication between cells of the immune system. Studies are proposed to characterize the metabolism of membrane phospholipids; including the effects of acute and chronic ethanol treatment on synthesis of ethanol lipids, phosphatidylethanol and fatty acid ethyl esters. Experiments are outlined to investigate the metabolism of ether linked phospholipids and associated arachidonic acid. The studies address the distribution of arachidonic within phospholipid classes as a possible regulatory mechanism for the synthesis two classes of bioactive lipids, eicosanoids and platelet activating factor. The effect of chronic ethanol exposure or leukocyte and lymphocyte function is considered in regards to altered membrane lipid composition prior to cell activation and aberrant phospholipid metabolism following cell activation. The consequences of two lipids which contain ethanol, phosphatidylethanol and fatty acid ethyl esters, on lymphocyte and leukocyte responses are considered.

本提案涉及乙醇对淋巴细胞和白细胞的影响 膜磷脂代谢作为异常免疫的一个组成部分 与慢性乙醇治疗相关的反应。 提案的基础 是考虑到特定的膜磷脂是必要的， “最佳”免疫反应 必要的膜磷脂或 它们可以存在于免疫细胞膜中，也可以作为免疫细胞膜产生。 对刺激的反应。 我们认为，乙醇改变免疫功能， 部分通过改变许多磷脂相关酶的活性 包括酰基转移酶、乙酰转移酶、磷酸胆碱 胞苷酰转移酶、胆碱磷酸转移酶、磷脂酶A2和 磷脂酶D 影响这些酶的结果 活动可能是产生一系列异常的脂质介质， 与淋巴细胞和白细胞功能相关的活化剂， 它们表达细胞表面抗原、运输离子、分泌 蛋白质，从而损害免疫系统细胞之间的通信。 研究提出了表征膜的代谢 磷脂;包括急性和慢性乙醇治疗的影响 乙醇脂类、磷脂酰乙醇和脂肪酸乙酯的合成 酯盐酸盐的褪概述了研究乙醚代谢的实验 连接的磷脂和相关的花生四烯酸。 这些研究涉及 花生四烯酸在磷脂类中的分布可能 两类生物活性脂质合成的调控机制， 类花生酸和血小板活化因子。 慢性酒精的影响 暴露或白细胞和淋巴细胞功能被认为是关于 在细胞活化之前改变的膜脂质组成和异常的 细胞活化后的磷脂代谢。 两个的后果 含有乙醇、磷脂酰乙醇和脂肪酸乙酯的脂质 酯，对淋巴细胞和白细胞的反应。