METABOLISM OF LEUKOTRIENE-B(4) BY GUINEA-PIG EOSINOPHILS

The metabolism of leukotriene B4 dihydroxy-6-cis-8,10-trans-14-cis-eic osatetraenoic acid) by isolated guinea pig eosinophils was investigate d. Incubation of guinea pig eosinophils with [H-3]-leukotriene B4 resu lted in the rapid conversion of leukotriene B4 to several more polar m etabolites. Two of these metabolites were identified by ultraviolet sp ectroscopy and gas chromatography-mass spectrometry as the omega oxida tion products (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-ei cosatetraenoic 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 -1,18-dicarboxylic-6,8,10,14,16-octadec apentaenoic acid (DELTA16,17-18-carboxy-19,20-dinor-leukotriene B4) we re tentatively identified. The identification of these compounds indic ates that guinea pig eosinophils are capable of metabolizing leukotrie ne B4 by both omega and beta oxidation. This catabolic activity may pl ay a role in modulating inflammatory reactions by removing the chemoat tractant leukotriene B4 from inflammatory sites.