Prescott S M
J Biol Chem. 1984 Jun 25;259(12):7615-21.
Eicosapentaenoic acid, which is a major fatty acid in fish oil, previously has been shown to competitively inhibit the cyclooxygenase-catalyzed metabolism of arachidonic acid in platelets. In the present study the effect of eicosapentaenoic acid on the production of leukotriene B via the lipoxygenase pathway in human neutrophils was examined. Eicosapentaenoate was incorporated into complex lipids of neutrophils at the same rate as arachidonate; release of the two homologous fatty acids in response to calcium ionophore A23187 was equivalent and both fatty acids were metabolized to a leukotriene B. The products derived from eicosapentaenoic acid were identified as leukotriene B5 and its stereoisomers. Eicosapentaenoate was a less favorable substrate for leukotriene B5 synthesis (94 ng/10(7) cells/5 min at 20 microM exogenous fatty acid) than arachidonate was for leukotriene B4 (401 ng under the same conditions). However, eicosapentaenoate or an oxygenated product inhibited arachidonate metabolism since at equimolar concentrations of eicosapentaenoate and arachidonate leukotriene B4 production was decreased by 68%. The inhibitory effect occurred at the level of leukotriene A hydrolase. The biological activity of eicosapentaenoate -derived products was tested; leukotriene B5 was found to have only approximately 10% of the potency of leukotriene B4 in inducing the aggregation of neutrophils, and the stereoisomers of leukotriene B5 were inactive. These data suggest that diets enriched in eicosapentaenoic acid affect neutrophils by decreasing the quantity of leukotriene B and by the production of a less potent leukotriene.
二十碳五烯酸是鱼油中的一种主要脂肪酸，此前已表明它能竞争性抑制血小板中环氧合酶催化的花生四烯酸代谢。在本研究中，检测了二十碳五烯酸对人中性粒细胞中通过脂氧合酶途径产生白三烯B的影响。二十碳五烯酸盐以与花生四烯酸盐相同的速率掺入中性粒细胞的复合脂质中；对钙离子载体A23187反应时，两种同源脂肪酸的释放量相当，且两种脂肪酸均代谢为白三烯B。源自二十碳五烯酸的产物被鉴定为白三烯B5及其立体异构体。与花生四烯酸盐对白三烯B4的合成（在相同条件下为401 ng）相比，二十碳五烯酸盐是白三烯B5合成的较不理想底物（在20 μM外源脂肪酸时为94 ng/10⁷细胞/5分钟）。然而，二十碳五烯酸盐或一种氧化产物抑制了花生四烯酸代谢，因为在等摩尔浓度的二十碳五烯酸盐和花生四烯酸盐时，白三烯B4的产生减少了68%。抑制作用发生在白三烯A水解酶水平。测试了源自二十碳五烯酸盐的产物的生物活性；发现白三烯B5在诱导中性粒细胞聚集方面的效力仅约为白三烯B4的10%，且白三烯B5的立体异构体无活性。这些数据表明，富含二十碳五烯酸的饮食通过减少白三烯B的量以及产生效力较低的白三烯来影响中性粒细胞。
