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 microM) 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.
Bozza
P T
PT
Immunopharmacology Laboratory, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil.
Weller
P F
PF
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001095:Arachidonic Acids / Q000378:metabolism*; D001241:Aspirin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007962:Leukocytes / Q000378:metabolism*; D050356:Lipid Metabolism; D009504:Neutrophils / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001095:Arachidonic Acids; C081565:arachidonyltrifluoromethane; D010741:Phospholipases A; D001241:Aspirin; D007052:Ibuprofen; D007213:Indomethacin