ROLE OF LEUKOTRIENES REVEALED BY TARGETED DISRUPTION OF THE 5-LIPOXYGENASE GENE
ROLE OF LEUKOTRIENES REVEALED BY TARGETED DISRUPTION OF THE 5-LIPOXYGENASE GENE
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DOI：
10.1038/372179a0
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发表时间：
1994-11-10
期刊：
影响因子：
64.8
通讯作者：
FUNK, CD
中科院分区：
文献类型：
--
作者：
CHEN, XS;SHELLER, JR;FUNK, CD
白三烯是一类有效的炎症和过敏反应生物介质（综述见参考文献1和2）。它们的生物合成来源于5-脂氧合酶催化的花生四烯酸在粒细胞、巨噬细胞和肥大细胞中的氧化。为了研究白三烯的生理重要性，我们通过胚胎干细胞中的同源重组破坏了5-脂氧合酶基因。5-脂氧合酶缺陷（5LX（-/-））小鼠发育正常，健康。他们有选择地反对某些煽动性的侮辱。虽然它们对内毒素休克的反应没有差异，但5LX（-/-）动物抵抗血小板活化因子诱导的休克的致死作用。对佛波醇酯引起的耳炎反应是正常的，而花生四烯酸引起的炎症则明显减少。在两种白细胞趋化模型中也发现了明显的差异。5LX（-/-）小鼠在损伤性损伤下的表型确定了白三烯在选定炎症状态的病理生理学中的作用。
LEUKOTRIENES constitute a class of potent biological mediators of inflammation and anaphylaxis (for reviews see refs 1 and 2). Their biosynthesis derives from 5-lipoxygenase-catalysed oxygenation of arachidonic acid in granulocytes, macrophages and mast cells. To examine the physiological importance of leukotrienes, we have disrupted the 5-lipoxygenase gene by homologous recombination in embryonic stem cells. 5-Lipoxygenase-deficient (5LX(-/-)) mice develop normally and are healthy. They show a selective opposition to certain inflammatory insults. Although there is no difference in their reaction to endotoxin shock, the 5LX(-/-) animals resist the lethal effects of shock induced by platelet-activating factor. Reaction to ear inflammation induced by phorbol ester is normal, whereas inflammation induced by arachidonic acid is markedly reduced. Contrasts mere also found in two models of leukocyte chemotaxis in vivo. The phenotype of 5LX(-/-) mice under injurious insult identifies the role for leukotrienes in the pathophysiology of select inflammatory states.