The human PMN leukocyte chemotactic activity of complex hydroxy-eicosatetraenoic acids (HETEs).

The human PMN leukocyte chemotactic activity of complex hydroxy-eicosatetraenoic acids (HETEs).
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复合羟基二十碳四烯酸 (HETE) 的人 PMN 白细胞趋化活性。

DOI:
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发表时间:
1980
影响因子:
4.4
通讯作者:
W. Pickett
W. Pickett
中科院分区:
医学2区
文献类型:
--
作者:
E. Goetzl;W. Pickett

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花生四烯酸在嗜碱性粒细胞、肥大细胞瘤细胞和其他白细胞中的脂氧合产生不稳定的中间体5-氢过氧-二十碳四烯酸,其部分转化为一系列具有额外极性取代基和3个共轭双键的复杂羟基-二十碳四烯酸(HETE)。其中一种产物5,12-di-HETE在低至3 ng/ml的浓度下对体外人中性粒细胞具有趋化性,并在30 ng/ml时引起最大中性粒细胞趋化反应,而5-HETE为1000 ng/ml,11-HETE和12-HETE为10,000 - 20,000 ng/ml。相反,同一系列中的其他产物,如缓慢反应物质5-羟基-6-谷胱甘肽-二十碳四烯酸(白三烯C)和血小板衍生的8,9,12-三羟基-二十碳三烯酸和8,11,12-三羟基-二十碳三烯酸仅表现出边缘中性粒细胞趋化活性。只有5,12-di-HETE从中性粒细胞释放了大量的β-葡萄糖醛酸苷酶和溶菌酶,但酶释放的最大水平远低于C5的趋化片段和甲酰-甲硫氨酰肽。
The lipoxygenation of arachidonic acid in basophils, mastocytoma cells, and other leukocytes generates the unstable intermediate 5-hydroperoxy-eicostaetraenoic acid, which is converted in part to a series of complex hydroxy-eicosatetraenoic acids (HETEs) with additional polar substituents and 3 conjugated double bonds. One of the products, 5,12-di-HETE, is chemotactic for human neutrophils in vitro at a concentration as low as 3 ng/ml and evokes a maximal neutrophil chemotactic response at 30 ng/ml, as compared to 1000 ng/ml for 5-HETE and 10,000 to 20,000 ng/ml for 11-HETE and 12-HETE. In contrast, other products in the same series, such as the slow reacting substance 5-hydroxy-6-glutathionyl-eicosatetraenoic acid (leukotriene C), and the platelet-derived 8,9,12-trihydroxy-eicosatrienoic acid and 8,11,12-trihydroxy-eicosatrienoic acid exhibited only marginal neutrophil chemotactic activity. Only 5,12-di-HETE released significant quantities of beta-glucuronidase and lysozyme from the neutrophils, but the maximal level of enzyme release was far less than that for the chemotactic fragment of C5 and the formyl-methionyl peptides.