Lysophosphatidylcholine stimulates phospholipase D activity in mouse peritoneal macrophages

Lysophosphatidylcholine (lysoPC) is a bioactive phospholipid that is involv ed in atherogenesis and inflammatory processes. However, the present unders tanding of mechanisms whereby lysophosphatidylcholine exerts its pathophysi ological actions is incomplete. La the present work, we show that lysoPC st imulates phospholipase D iPLD activity in mouse peritoneal macrophages, PLD activation leads to the generation of important second messengers such as phosphatidic acid, lysophosphatidic acid, and diacylglycerol, all of which can regulate cellular responses involved in atherogenesis and inflammation. The activation of PLD by lysoPC was attenuated by down-regulation of prote in kinase C activity with prolonged incubation with 100 nm of 4 beta-phorbo l 12-myristate 13-acetate (PMA). Preincubation of the macrophages with the tyrosine kinase inhibitor genistein decreased the stimulation of PLD by lys oPC, while pretreatment with orthovanadate, which inhibits tyrosine phospha tases, enhanced basal and lysoPC-stimulated PLD activity The activation of PLD by lysoPC was attenuated by the platelet activating factor (PAF) recept or antagonist WEB-2086, suggesting a role for PAF receptor activation in th is process. Furthermore, acetylation of lysoPC substantially increased its potency in activating PLD, suggesting that a cellular metabolite of lysoPC such as 1-acetyl 2-acetyl PC might be responsible for at least part of the effect of lysoPC on Lysophosphatidylcholine stimulates phospholipase D acti vity in mouse peritoneal macrophages.