ETHANOL SUPPRESSION OF IMMUNA RESPONSE

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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.