Monohydroxyeicosatetraenoic acids (HETEs) induce degranulation of human neutrophils.
Monohydroxyeicosatetraenoic acids (HETEs) induce degranulation of human neutrophils.
复制标题
单羟基二十碳四烯酸 (HETE) 诱导人中性粒细胞脱粒。
DOI：
10.4049/jimmunol.124.5.2100
复制
发表时间：
1980
影响因子：
4.4
通讯作者：
C. Parker
中科院分区：
文献类型：
--
作者：
W. Stenson;C. Parker
通过生物合成方法制备了神经细胞中的脂氧合酶产物 5-S-羟基-6,8,11,14-二十碳四烯酸 (5-HETE) 和血小板中的脂氧合酶产物 12-L-羟基-5,8,10,14-二十碳四烯酸 (12-HETE)，并与纯化的人外周血一起孵育 中性粒细胞。 5-HETE 和 12-HETE 在 5-10-μM 浓度下均诱导特定颗粒脱粒。在这些浓度下，5-HETE 和 12-HETE 对中性粒细胞都有趋化作用。花生四烯酸是 5-HETE 和 12-HETE 的代谢前体，不会诱导脱粒。钙离子载体 A23187 诱导中性粒细胞脱颗粒，并激活中性粒细胞中的花生四烯酸代谢，从而产生 5-HETE。离子载体诱导的 5-HETE 产生和离子载体诱导的脱颗粒都可以被 5,8,11,14-二十碳四烯酸（一种花生四烯酸代谢抑制剂）抑制，具有非常相似的抑制曲线。我们认为 5-HETE 和 12-HETE 诱导的脱粒机制是膜磷脂脂肪酸组成的改变。
5-S-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE), a lipoxygenase product in neurophils, and 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE), a lipoxygenase product in platelets, were prepared biosynthetically and incubated with purified human peripheral neutrophils. Both 5-HETE and 12-HETE at 5- to 10-microM concentrations induced degranulation of specific granules. Both 5-HETE and 12-HETE are chemotactic for neutrophils at these concentrations. Arachidonic acid, the metabolic precursor of 5-HETE and 12-HETE, did not induce degranulation. The calcium ionophore A23187 induces neutrophils degranulation and also activates arachidonic acid metabolism in neutrophils resulting in 5-HETE production. Both ionophore-induced 5-HETE production and ionophore-induced degranulation can be inhibited, with very similar inhibition curves, by 5,8,11,14-eicosatetraynoic acid, an inhibitor of arachidonate metabolism. We propose that the mechanism for 5-HETE- and 12-HETE-induced degranulation is an alteration in the fatty acid composition of membrane phospholipids.