ETHANOL SUPPRESSION OF IMMUNE RESPONSE

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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.