Leukotriene generation by eosinophils.
Horse eosinophils purified to greater than 98% generated slow reacting substance (SRS) when incubated with the calcium ionophore A23187. On a per cell basis, eosinophils generated four to five times the SRS produced by similarly treated horse neutrophils. Eosinophil SRS production was inhibited by 5,8,11,14-eicosatetraynoic acid and augmented by indomethacin and arachidonic acid, suggesting that it was a product(s) of the lipoxygenase pathway of arachidonic acid metabolism. Compounds with SRS activity were purified by high-pressure liquid chromatography (HPLC) and identified by ultraviolet spectra, spectral shift on treatment with lipoxygenase, incorporation of [14C]arachidonic acid, gas chromatography-mass spectrometry, and comparison of retention times on HPLC to authentic standards. The eosinophil products characterized were 5-(S), 12-(R)-dihydroxy-6-cis-8, 10-trans-14-cis-eicosatetraenoic acid (leukotriene B4) and its 5-(S), 12-(R)-6-trans and 5-(S), 12-(S)-6-trans isomers, 5-(S)-hydroxy-6-(R)-S-glutathionyl-7,9-trans-11, 14-cis-eicosatetraenoic acid (leukotriene C4) and its 11-trans isomer, and 5-(S)-hydroxy-6-(R)-S-cysteinylglycine-7,9-trans-11,14-cis-eicosatetraenoic acid (leukotriene D4).
D000818:Animals; D001095:Arachidonic Acids / Q000096:biosynthesis* / Q000302:isolation & purification; D012898:Autacoids / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D004804:Eosinophils / Q000378:metabolism*; D006168:Guinea Pigs; D006736:Horses; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007975:Leukotriene B4; D051379:Mice; D008815:Mice, Inbred Strains; D009504:Neutrophils / Q000378:metabolism; D013189:SRS-A / Q000096:biosynthesis / Q000302:isolation & purification
D001095:Arachidonic Acids; D012898:Autacoids; D002867:Chromones; D013189:SRS-A; D007975:Leukotriene B4; D000001:Calcimycin; C006312:FPL 55712; D007770:L-Lactate Dehydrogenase