Metabolism of leukotriene B4 by guinea pig eosinophils

The metabolism of leukotriene B4 (5(S),12(R)-dihydroxy-6-cis-8,10-trans-14-cis-eicosatetraenoic acid) by isolated guinea pig eosinophils was investigated. Incubation of guinea pig eosinophils with [3H]-leukotriene B4 resulted in the rapid conversion of leukotriene B4 to several more polar metabolites. Two of these metabolites were identified by ultraviolet spectroscopy and gas chromatography-mass spectrometry as the omega oxidation products 5(S),12(R),20-trihydroxy-6,8,10,14-eicosatetraenoic acid (20-hydroxy-leukotriene B4) and 5(S),12(R),19-trihydroxy-6,8,10,14- eicosatetraenoic acid (19-hydroxy-leukotriene B4). Two novel metabolites, 5(S),12(R),18,19-tetrahydroxy-6,8,10,14 eicosatetraenoic acid (18,19-dihydroxy-leukotriene B4) and 5(S),12(R)-dihydroxy-1,18-dicarboxylic-6,8,10,14,16-octadecapentaenoi c acid (delta 16,17-18-carboxy-19,20-dinor-leukotriene B4) were tentatively identified. The identification of these compounds indicates that guinea pig eosinophils are capable of metabolizing leukotriene B4 by both omega and beta oxidation. This catabolic activity may play a role in modulating inflammatory reactions by removing the chemoattractant leukotriene B4 from inflammatory sites.