Tissue factor expression of human monocytes is suppressed by lysophosphatidylcholine.
The expression of tissue factor (TF), the principal initiator of coagulation, is increased during inflammation and atherosclerosis. Both conditions are promoted by lysophosphatidylcholine (lysoPC). We observed in the present study that lysoPC (1 to 10 micromol/L) dose-dependently reduced TF activity in human monocytes, as elicited by lipopolysaccharide (LPS). Lysophosphatidylethanolamine (lysoPE) and other lysophospholipids did not affect LPS-induced TF activity of human monocytes. TF antigen expression as elicited by LPS was also lowered by lysoPC. Phospholipid analyses indicated a selective increase 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 receptors and internalization of LPS into monocytes were not affected by lysoPC. In contrast, LPS-mediated nuclear binding of nuclear factor-kappaB/Rel to a TF-specific kappaB site was inhibited by lysoPC. Induction of TF mRNA expression by LPS tended to be partially reduced by the lysophospholipid. Preincubation with lysoPC increased monocytic cAMP levels. Inhibition of adenylyl cyclase by pretreatment with 2'-deoxy-3'-adenosine monophosphate partially 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 posttranscriptional mechanisms. LysoPC may thus attenuate activation of coagulation during inflammation and atherosclerosis.
Engelmann
B
B
Physiologisches Institut der Universität München, Munich, Germany. Bernd.Engelmann@med.uni-muenchen.de
Zieseniss
S
S
Brand
K
K
Page
S
S
Lentschat
A
A
Ulmer
A J
AJ
Gerlach
E
E
D000067956:Adenylyl Cyclase Inhibitors; D015152:Blotting, Northern; D003994:Bucladesine / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D003838:Deoxyadenine Nucleotides / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D009000:Monocytes / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013925:Thromboplastin / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*
D000067956:Adenylyl Cyclase Inhibitors; D003838:Deoxyadenine Nucleotides; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D008244:Lysophosphatidylcholines; D016328:NF-kappa B; D012333:RNA, Messenger; C028191:2'-deoxy-3'-adenosine monophosphate; D003994:Bucladesine; D013925:Thromboplastin; D000242:Cyclic AMP