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.
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