Lipoxygenase products modulate histamine release in human basophils
Lipoxygenase products modulate histamine release in human basophils
复制标题
脂氧合酶产品调节人嗜碱性粒细胞中的组胺释放
DOI：
10.1038/292455a0
复制
发表时间：
1981
期刊：
影响因子：
64.8
通讯作者：
L. Lichtenstein
中科院分区：
文献类型：
--
作者：
S. Peters;M. Siegel;A. Kagey;L. Lichtenstein
从细胞磷脂中释放的花生四烯酸由两种主要的酶系统代谢1。环加氧酶途径负责产生前列腺素、血栓素和前列环素，而脂氧合酶途径形成一系列单过氧和单羟基二十碳四烯酸。5-脂氧合酶途径最终导致产生白三烯B（已知最有效的趋化分子之一）和SRS-A（过敏反应的慢反应物质-白三烯C和D）。我们对脂氧合酶的早期研究表明，脂氧合酶的产物对于从人嗜碱性粒细胞释放组胺和钝化内源性控制机制都是必需的2 -4。为了验证这一假设，我们研究了外源性添加的脂氧合酶途径的产物对抗原诱导的组胺释放的人嗜碱性白细胞在体外的效果。本报告表明，5-氢过氧二十碳四烯酸（5-HPETE），在亚微摩尔浓度，引起剂量依赖性的组胺释放的增强和逆转的抑制组胺释放所引起的激素和其他激动剂，通过腺苷酸环化酶的作用。5-HPETE的还原产物5-羟基二十碳四烯酸（5-HETE）具有这两种活性，但效力低约3至10倍。
Arachidonic acid released from cellular phospholipids is metabolized by two major enzyme systems1. The cyclo-oxygenase pathways are responsible for the production of prostaglandins, thromboxanes and prostacyclin while the lipoxygenase pathways form a series of monoperoxy- and monohydroxyeicosatetraenoic acids. The 5-lipoxygenase pathway eventually leads to the production of both leukotriene B, one of the most potent chemotactic molecules known, and SRS-A (slow-reacting substance of anaphylaxis—leukotrienes C and D). Our earlier studies of the lipoxygenase enzyme(s) suggested that a product (s) of lipoxygenase (s) is both necessary for histamine release from human basophils and blunts endogenous control mechanisms2–4. To test this hypothesis, we have studied the effect of exogenously added products of lipoxygenase pathways on antigen-induced histamine release from human basophilic leukocytes in vitro. The present report demonstrates that 5-hydroperoxyeicosatetraenoic acid (5-HPETE), at sub-micromolar concentrations, causes both a dose-dependent enhancement of histamine release and a reversal of the inhibition of histamine release caused by hormones and other agonists which act via adenylate cyclase. The reduced product of 5-HPETE, 5-hydroxyeicosatetraenoic acid (5-HETE) has both activities, but is approximately 3 to 10 times less potent.