Effects of inhibitors of arachidonic acid metabolism on thromboplastin activity in human monocytes.
Human isolated monocytes possess low levels of procoagulant activity, which was stimulated 10-30 fold by brief (2 hr) exposure to 10 micrograms/ml endotoxin. This activity was expressed in normal or factor XII-deficient plasma, but lost in plasma deficient in factors X or VII, indicating that it was due to thromboplastin. The stimulation of monocyte thromboplastin by endotoxin was inhibited in a dose-dependent manner by two phospholipase A2 inhibitors, 4-bromophenacyl bromide and quinacrine, and by two lipoxygenase inhibitors, eicosatetraynoic acid and nordihydroguaiaretic acid. Two cyclooxygenase inhibitors, aspirin and indomethacin, prevented endotoxin-induced increases in thromboxane B2 production but had no effect on thromboplastin production. These results suggest that a component in the sequence of lipid deacylation, arachidonic acid release, and metabolism via lipoxygenase may mediate the stimulation of monocyte thromboplastin activity by endotoxin.
D001091:Arachidonate Lipoxygenases; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors*; D016861:Cyclooxygenase Inhibitors; D004731:Endotoxins / Q000494:pharmacology; D005168:Factor VII Deficiency / Q000097:blood; D005171:Factor X Deficiency / Q000097:blood; D006801:Humans; D016859:Lipoxygenase Inhibitors; D009000:Monocytes / Q000378:metabolism*; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D013925:Thromboplastin / Q000378:metabolism*; D013929:Thromboxane B2 / Q000097:blood
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D004731:Endotoxins; D016859:Lipoxygenase Inhibitors; D016718:Arachidonic Acid; D013929:Thromboxane B2; D013925:Thromboplastin; D001091:Arachidonate Lipoxygenases; D010741:Phospholipases A; D054467:Phospholipases A2