Alteration of uptake and distribution of eicosanoid precursor fatty acids by aspirin

Aspirin is an important drug in the treatment of numerous disorders, especially rheumatic diseases. Its several mechanisms of action include inhibition of prostaglandin production by acetylation of prostaglandin synthetase. To explore further the modulatory effect of aspirin on eicosanoid production, we examined its effect on uptake and incorporation of fatty acids into phospholipids of human peripheral blood monocytes. Aspirin ingestion by normal volunteers inhibited uptake of arachidonic acid and linoleic acid in monocytes cultured for 3 days. Similar inhibition was observed when cultured normal human peritoneal macrophages were treated with aspirin for 3 days. In contrast, monocytes cultured for 12 days from both normal volunteers who had ingested aspirin and normal cells treated with aspirin in vitro for the first 3 days of a 12-day culture period expressed an increased uptake of both arachidonic and linoleic acids. Similarly, incorporation of fatty acid into phosphatidylcholine was depressed in 3-day cultured cells but was increased in 12-day cultured cells. Thus, aspirin, whether administered in vivo or added in vitro, modulates cellular uptake and incorporation of eicosanoid precursor fatty acids and their insertion into membrane phospholipids in cultured human monocytes and macrophages.