The role of arachidonic acid release and lipoxygenase pathway in lipopolysaccharide-induced thromboplastin activity in monocytes.
Lipopolysaccharide (LPS) stimulation of human monocytes in heparinized whole blood in vitro as expressed by induced activity of thromboplastin, has been studied. An essential role of arachidonic acid (20:4) release was found. 2,4'-Dibromoacetophenone, a phospholipase A2 inhibitor, totally blocked the induced synthesis of thromboplastin activity. Furthermore, nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, had an effect on the LPS-induced thromboplastin synthesis which varied from no inhibition in individuals insensitive to LPS ('low responders'), up to 80% inhibition in the person with the highest response ('high responder') to LPS. Platelets were found to be partially responsible for this difference. Thus, monocytes from high responders cross-combined with platelets from low responders were much less prone to LPS stimulation than they were in the presence of high responder platelets. Intake of acetylsalicylic acid caused a 50% increment of LPS-induced thromboplastin synthesis, and this effect was mediated by platelets.
Osterud
B
B
Institute of Medical Biology, University of Tromsø, Norway.
Olsen
J O
JO
Wilsgård
L
L
D000098:Acetophenones / Q000494:pharmacology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood*; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000502:physiology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008084:Lipoxygenase / Q000097:blood*; D016859:Lipoxygenase Inhibitors; D009637:Masoprocol / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D013925:Thromboplastin / Q000096:biosynthesis*
D000098:Acetophenones; D001095:Arachidonic Acids; D008070:Lipopolysaccharides; D016859:Lipoxygenase Inhibitors; D016718:Arachidonic Acid; D009637:Masoprocol; D013925:Thromboplastin; D008084:Lipoxygenase; D010741:Phospholipases A; D054467:Phospholipases A2; C006821:4-bromophenacyl bromide; D001241:Aspirin