A novel metabolic pathway for leukotriene B4 in different cell types: primary reduction of a double bond

Addition of leukotriene B4 together with trace amounts of tritiated leukotriene B4 to different cell types, such as bone marrow-derived macrophages, T-lymphocytes, mesangial cells or fibroblast tumor cells, led to the formation of several hitherto unknown degradation products within hours. None of them could be identified as 20-hydroxy- or 20-carboxyleukotriene B4, known to be produced by polymorphonuclear leukocytes. The primarily formed transient leukotriene B4 metabolite was less polar than leukotriene B4 and was detectable by measuring its ultraviolet absorbance at 232 nm or its radioactivity. Mass spectral analysis showed very similar fragmentation spectra of leukotriene B4 and its primary metabolite. The most abundant ion and the main fragments of the new metabolite were increased by two mass units compared to leukotriene B4. These observations suggest that, in a variety of cells, leukotriene B4 is first reduced to a 5,12-dihydroxyeicosatrienoic acid, which is further converted to secondary hydrophilic degradation products. This raises the question of the major route of leukotriene B4 metabolism in vivo.