Novel pathway for the metabolism of 6-trans-leukotriene B4 by human polymorphonuclear leukocytes

Polymorphonuclear leukocytes convert arachidonic acid to leukotriene B4 as well as to two 6-trans isomers of this substance. Both leukotriene B4 and 6-trans-leukotriene B4 are metabolized by a hydroxylase in human polymorphonuclear leukocytes to 20-hydroxy metabolites. We have now found a second, previously unknown, metabolic pathway for 6-trans-leukotriene B4 involving reduction of either the 6- or the 10- double bond. One of the two major metabolites of 6-trans-leukotriene B4 in human polymorphonuclear leukocytes is formed by the action of this reductase, followed by hydroxylation by leukotriene B4 20-hydroxylase. On the basis of ultraviolet (maximum absorbance at 232 nm) and mass spectral evidence, this product is either 5,12,20-trihydroxy-6,8,14-eicosatrienoic acid or 5,12,20-trihydroxy-8,10,14-eicosatrienoic acid.