title: The role of arachidonic acid release and lipoxygenase pathway in lipopolysaccharide-induced thromboplastin activity in monocytes.
abstract: 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.
authors: Institute of Medical Biology, University of Tromsø, Norway.
authors: B
authors: B
authors: Osterud
authors: J O
authors: JO
authors: Olsen
authors: L
authors: L
authors: Wilsgård
mesh_terms: 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*
chemical_list: 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