Formation of a novel 20-hydroxylated metabolite of lipoxin A₄ by human neutrophil microsomes

Lipoxin A₄ (LXA₄) is a biologically active compound produced from arachidonic acid via interactions of lipoxygenases. Incubation of LXA₄ either with human neutrophils or with the neutrophil microsomes leads to formation of a polar compound on a reverse-phase high-performance liquid chromatography. We have identified the metabolite as 20-hydroxy-LXA₄, a novel metabolite of arachidonic acid, on the basis of ultraviolet spectrometry and gas chromatography-mass spectrometry. The LXA₄ω -hydroxylation requires both molecular oxygen and NADPH, and is inhibited by carbon monoxide, by antibodies raised against NADPH-cytochrome P-450 reductase, or competitively by leukotriene B₄ (LTB₄) and LTB₅, substrates of LTB₄ ω-hydroxylase. These findings indicate that the formation of 20-hydroxy-LXA₄ is catalyzed by a neutrophil cytochrome P-450, the LTB₄ ω-hydroxylase.