Hydroxyeicosatetraenoic acids and other unsaturated fatty acids inhibit endotoxin-induced thromboplastin activity in human monocytes.
Human peripheral blood monocytes possessed increased thromboplastin activity when exposed to 10 micrograms/ml of bacterial endotoxin for 2 h. The effects of endotoxin were strongly inhibited by 10-20 microM of several unsaturated fatty acids: arachidonic, dihomo-gamma-linolenic, linoleic, linolenic and oleic acids. Two saturated fatty acids, arachidic and stearic acids, produced minimal inhibition at 20 microM. Three lipoxygenase-derived hydroxyfatty acids were also inhibitory, with IC50 values of 10 microM (5- and 12-hydroxyeicosatetraenoic acids) and 20 microM (15-hydroxyeicosatetraenoic acid). Leukotriene B4, 1 nM to 1 microM, was inactive. None of the fatty acids affected the ability of standard thromboplastin to shorten the clotting time of normal plasma or affected the activity of endotoxin as measured by a Limulus clotting assay.
Crutchley
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D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D004537:Eicosanoic Acids / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007975:Leukotriene B4 / Q000494:pharmacology; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology; D008042:Linolenic Acids / Q000494:pharmacology; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D013229:Stearic Acids / Q000494:pharmacology; D013925:Thromboplastin / Q000378:metabolism*; D017962:alpha-Linolenic Acid
D001095:Arachidonic Acids; D004537:Eicosanoic Acids; D004731:Endotoxins; D005231:Fatty Acids, Unsaturated; D006893:Hydroxyeicosatetraenoic Acids; D008041:Linoleic Acids; D008042:Linolenic Acids; D009829:Oleic Acids; D013229:Stearic Acids; D017962:alpha-Linolenic Acid; D007975:Leukotriene B4; D016718:Arachidonic Acid; D019301:Oleic Acid; C031183:stearic acid; D013925:Thromboplastin; D019787:Linoleic Acid; D007213:Indomethacin