Cytochrome P-450 CYP4F3A catalyzes the inactivation of leukotriene B-4 by omega-hydroxylation, an activity of which is specifically expressed in human neutrophils. Here, we examined expression of the LTB4 omega-hydroxylating activity during the differentiation of HL60 cells, an acute promyelocytic leukemia cell line, in the presence of various inducers. Among the inducers used, all-transretinoic, acid (ATRA) most strongly induces the LTB4 omega-hydroxylating activity in a dose-dependent manner. The time course of the induction of the omega-hydroxylating activity correlates well with that of the superoxide-generating activity, indicative of cell differentiation. ATRA-treated cell microsomes convert LTB4 to its 20-hydroxyl derivative under aerobic conditions in the present of NADPH. The reaction is inhibited by carbon monoxide, an inhibitor of cytochrome P-450, and by antibodies raised against NADPH-P-450 reductase. CYP4F3A appears to be responsible for the LTB4 omega-hydroxylase activity, based on the following observations: expression of the mRNA for CYP4173A is observed together with the induction of LTB4 omega-hydroxylating activity in ATRA-treated HL60 cells; and the apparent K-m values for the omega-hydroxylation of LTB4 and lipoxin B-4 by ATRA-treated cell microsomes are essentially the same as those of CYP4173A in human neutrophil microsomes. (C) 2003 Elsevier Inc. All rights reserved.