The effect of ethanol on arachidonic acid metabolism in the murine peritoneal macrophage.
Exposure to ethanol in man has been linked to an alteration of the immune surveillance system and reduced ability of the macrophage to undergo phagocytosis. Since ethanol has been suggested to alter membrane function and inhibit the production of calcium ionophore stimulated synthesis of prostaglandins and leukotrienes by the human neutrophil and transformed murine mast cell, the dose response effect of ethanol on the biosynthesis of icosanoids by the peritoneal macrophage during zymosan phagocytosis was studied. Peritoneal macrophages from two inbred strains of mice derived from a common stock (HS) and selected for sensitivity to ethanol (short sleep [SS]/long sleep [LS]) were studied. Zymosan phagocytosis was found to lead to synthesis of LTC4 (70 ng/10(6) cells), 6-keto-PGF1 alpha (5 ng/10(6) cells) and PGE2 (3 ng/10(6) cells). For the HS macrophage, ethanol caused a dose dependent inhibition of these lipid mediators as well as inhibition of phagocytosis and release of beta-hexosaminidase. However, a difference was observed in arachidonate metabolism stimulated by phagocytosis between the LS and SS mice below 100 mM ethanol. The SS mouse had a 50% inhibition of cyclooxygenase products at 86 mM ethanol with no inhibition of lipoxygenase metabolites. The LS mice had a trend suggesting increased lipoxygenase metabolites below 100 mM ethanol. At these levels of ethanol which can be found in man, these results suggest there may be differential production of lipid mediators under genetic control.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010587:Phagocytosis; D011453:Prostaglandins / Q000096:biosynthesis; D013189:SRS-A / Q000096:biosynthesis
D001095:Arachidonic Acids; D011453:Prostaglandins; D013189:SRS-A; D016718:Arachidonic Acid; D000431:Ethanol