LEUKOCYTE LIPID BODY FORMATION AND EICOSANOID GENERATION - CYCLOOXYGENASE-INDEPENDENT INHIBITION BY ASPIRIN

Lipid bodies, cytoplasmic inclusions that develop in cells associated with inflammation, are inducible structures that might participate in generating inflammatory eicosanoids, Cis-unsaturated fatty acids (arac hidonic and oleic acids) rapidly induced lipid body formation in leuko cytes, and this lipid body induction was inhibited by aspirin and nons teroidal antiinflammatory drugs (NSAIDs), Several findings indicated t hat the inhibitory effect of aspirin and NSAIDs on lipid body formatio n was independent of cyclooxygenase (COX) inhibition, First, the non-C OX inhibitor, sodium salicylate, was as potent as aspirin in inhibitin g lipid body formation elicited by cis-fatty acids, Second, cis-fatty acid-induced lipid body formation was not impaired in macrophages from COX-1 or COX-2 genetically deficient mice, Finally, NSAIDs inhibited arachidonic acid-induced lipid body formation likewise in macrophages from wild-type and COX-1- and COX-2-deficient mice, An enhanced capaci ty to generate eicosanoids developed after 1 hr concordantly with cis- fatty acid-induced lipid body formation, Arachidonic and oleic acid-in duced lipid body numbers correlated with the enhanced levels of leukot rienes B-4 and C-4 and prostaglandin E(2) produced after submaximal ca lcium ionophore stimulation, Aspirin and NSAIDs inhibited both induced lipid body formation and the enhanced capacity for forming leukotrien es as well as prostaglandins. Our studies indicate that lipid body for mation is an inducible early response in leukocytes that correlates wi th enhanced eicosanoid synthesis, Aspirin and NSAIDs, independent of C OX inhibition, inhibit cis-fatty acid-induced lipid body formation in leukocytes and in concert inhibit the enhanced synthesis of leukotrien es and prostaglandins.