Inhibition of ionophore-stimulated leukotriene B4 production in human leucocytes by monohydroxy fatty acids.
Leukotriene B4 (LTB4) release by calcium ionophore-stimulated human leucocytes was measured by use of selective solvent partition of reaction mixtures and an agarose microdroplet chemokinesis assay, and the inhibitory effects of four monohydroxy fatty acids were determined. 15-Hydroxy-eicosatetraenoic acid (15-HETE) was the most effective inhibitor of LTB4 production with an approximate IC50 value of 6 microM and 99% inhibition at 50 microM, whereas 13-hydroxy-octadecadienoic acid (13-HODD) and 12-HETE were weaker inhibitors with approximate IC50 values of 32 microM and 23 microM, and 59% and 68% inhibition at 50 microM, respectively. We suggest that 13-HODD and 12-HETE, which are present in large amounts in the lesions of the skin disease psoriasis, may act as endogenous modulators of 5-lipoxygenase activity in skin.
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001091:Arachidonate Lipoxygenases; D000001:Calcimycin / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006880:Hydroxy Acids / Q000494:pharmacology*; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D007975:Leukotriene B4 / Q000096:biosynthesis*; D008041:Linoleic Acids / Q000494:pharmacology; D044243:Linoleic Acids, Conjugated; D008084:Lipoxygenase / Q000378:metabolism; D012867:Skin / Q000201:enzymology; D013997:Time Factors
D006880:Hydroxy Acids; D006893:Hydroxyeicosatetraenoic Acids; D008041:Linoleic Acids; D044243:Linoleic Acids, Conjugated; C024347:9-hydroxy-10,12-octadecadienoic acid; D007975:Leukotriene B4; D000001:Calcimycin; C024348:13-hydroxy-9,11-octadecadienoic acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D001091:Arachidonate Lipoxygenases; D008084:Lipoxygenase