Arachidonyl trifluoromethyl ketone induces lipid body formation in leukocytes

Leukocyte lipid bodies, abundant in cells associated with inflammation, can be induced to form in response to stimuli that include cis-unsaturated, but not saturated, fatty acids. Arachidonyl trifluoromethyl ketone (AACOCF(3)), a non-esterifiable arachidonate analog and an inhibitor of cytosolic phospholipase A(2) enzymes (PLA(2)), dose-dependently (0-20 muM) stimulated neutrophil lipid body formation, but this stimulation was not attributable to PLA(2) inhibition. Palmitoyl trifluoromethyl ketone, also a PLA(2) inhibitor, failed to stimulate lipid body formation, like palmitic acid itself, and did not inhibit stimulated lipid body formation. Moreover, aspirin, indomethacin and ibuprofen, which inhibit cis-unsaturated fatty acid-induced lipid body formation, inhibited AACOCF(3)-induced lipid body formation. Lipid body induction with AACOCF(3) reflected its structural basis as a cis-unsaturated fatty acid analog. These results indicate that cytosolic PLA(2) enzymes are not active in lipid body induction and cis-fatty acid stimulation of lipid body formation does not require esterification of cis-fatty acids into glycerolipids. (C) 2001 Harcourt Publishers Ltd.