The interaction of ethanol and exogenous arachidonic acid in the generation of extracellular messengers by mouse peritoneal macrophages.
It is increasingly recognized that macrophages play a crucial role in the development of chronic inflammatory states such as alcoholic liver disease. These cells can metabolize free arachidonic acid in the absence of a discernible trigger. The present study was undertaken to examine the short-term effects of ethanol on the generation of these exogenous arachidonate-derived extracellular mediators. Ethanol caused a dose-dependent decrease in the production of both cyclooxygenase and lipoxygenase metabolites. Similar effects were observed on the esterification of exogenous arachidonate into cellular lipids. To characterize further the effects of ethanol on exogenous arachidonic acid metabolism, we studied the short-term responses displayed by macrophages challenged with another soluble stimulus; the tumor-promoting agent phorbol myristate acetate. We observed an inhibition by ethanol of the superoxide anion response triggered by phorbol myristate acetate similar to that observed for exogenous arachidonate oxygenation. Our results show that ethanol can inhibit these soluble stimuli-elicited responses, possibly through its disorganizing effect on plasma membrane.
Balsinde
J
J
Unidad de Lípidos, Hospital Clínico de San Carlos, Universidad Complutense de Madrid, Spain.
Schüller
A
A
Diez
E
E
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D066298:In Vitro Techniques; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D010529:Peritoneal Cavity / Q000166:cytology; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D013481:Superoxides; D016718:Arachidonic Acid; D000431:Ethanol; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D013755:Tetradecanoylphorbol Acetate