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

[摘要]

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.

[学科分类] 生物化学/生物物理

[关键词] Lipoxin A4;ω-Hydroxylation;Cytochrome P-450;Human neutrophil;LXA4;lipoxin A4 or (5S;6R;15S)-5;6;15-trihydroxy-7;9;11;13-E;E;Z;E-eicosatetraenoic acid;20-OH-LXA4;20-hydroxy-LXA4 or (5S;6R;15S)-5;6;15;20-tetrahydroxy-7;9;11;13-E;E;Z;E-eicosatetraenoic acid;LXB4;lipoxin B4;LTB4;leukotriene B4;20-OH-LTB4;20-hydroxy-LTB4;PGA1 prostaglandins A1;P-450;cytochrome P-450;P-450LTBω;cytochrome P-450LTBω or human neutrophil LTB4 ω-hydroxylase.