Tissue factor expression of human monocytes is suppressed by lysophosphatidylcholine

The expression of tissue factor (TF), the principal initiator of coagulatio n, is increased during inflammation and atherosclerosis. Both conditions ar e promoted by lysophosphatidylcholine (lysoPC). We observed in the present study that lysoPC (I to 10 mu mol/L) dose-dependently reduced TF activity i n human monocytes, as elicited by lipopolysaccharide (LPS). Lysophosphatidy lethanolamine (lysoPE) and other lysophospholipids did not affect LPS-induc ed TF activity of human monocytes. TF antigen expression as elicited by LPS was also lowered by lysoPC. Phospholipid analyses indicated a selective in crease in the lysoPC content of the monocytes after preincubation with the lysophospholipid. LysoPC inhibited the TF activity of Mono Mac-6 cells to a similar extent as in the monocytes. LPS binding to plasma membrane recepto rs and internalization of LPS into monocytes were not affected by lysoPC. I n contrast, LPS-mediated nuclear binding of nuclear factor-kappa B/Rel to a TF-specific kappa B Site was inhibited by lysoPC. Induction of TF mRNA exp ression by LPS tended to be partially reduced by the lysophospholipid. Prei ncubation with lysoPC increased monocytic cAMP levels. Inhibition of adenyl yl cyclase by pretreatment with 2'-deoxy-3'-adenosine monophosphate partial ly reversed the inhibition of TF activity promoted by lysoPC. In conclusion , lysoPC markedly decreases LPS-mediated TF expression of human monocytes, the effect probably being mediated by both transcriptional and posttranscri ptional mechanisms. LysoPC may thus attenuate activation of coagulation dur ing inflammation and atherosclerosis.