LTA4-derived 5-oxo-eicosatetraenoic acid:: pH-dependent formation and interaction with the LTB4 receptor of human polymorphonuclear leukocytes

被引：7

作者：

Falgueyret, JP ^{[1
]}

Riendeau, D ^{[1
]}

机构：

[1] Merck Frosst Ctr Therapeut Res, Dept Biochem & Mol Biol, Kirkland, PQ H9H 3L1, Canada

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS | 2000年 / 1484卷 / 01期

关键词：

5-oxo-(7E; 9E; 11Z; 14Z)-eicosatetraenoic acid; leukotriene A(4); leukotriene B-4; leukotriene B-4 receptor; calcium mobilization;

D O I：

10.1016/S1388-1981(99)00198-5

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

5-Oxo-(7E,9E,11Z,14Z)-eicosatetraenoic acid (5-oxo-ETE) has been identified as a non-enzymatic hydrolysis product of leukotriene A(4) (LTA(4)) in addition to 5,12-dihydroxy-(6E,8E,10E,14Z)-eicosatetraenoic acids (5,12-diHETEs) and 5,6-dihydroxy-(7E,9E,11Z,14Z)-eicosatetraenoic acids (5,6-diHETEs). The amount of 5-oxo-ETE detected in the mixture of the hydrolysis products of LTA(4) was found to be pH-dependent. After incubation of LTA(4) in aqueous medium, the ratio of 5-oxo-ETE to 5,12-diHETE was 1:6 at pH 7.5, and 1:1 at pH 9.5. 5-Oxo-ETE was isolated from the alkaline hydrolysis products of LTA(4) in order to evaluate its effects on human polymorphonuclear (PMN) leukocytes. 5-Oxo-ETE induced a rapid and dose-dependent mobilization of calcium in PMN leukocytes with an EC50 of 250 nM, as compared to values of 3.5 nM for leukotriene B-4 (LTB4) and >500 nM for 5(S)-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoic acid (5-HETE). Pretreatment of the cells with LTB4 totally abolished the calcium response induced by 5-oxo-ETE. In contrast, the preincubation with 5-oxo-ETE did not affect the calcium mobilization induced by LTB4. The calcium response induced by 5-oxo-ETE was totally inhibited by the specific LTB4 receptor antagonist LY223982. These data demonstrate that 5-oxo-ETE can induce calcium mobilization in PMN leukocyte via the LTB4 receptor in contrast to the closely related analog 5-oxo(6E,8Z,11Z,14Z)-eicosatetraenoic acid which is known to activate human neutrophils by a mechanism independent of the receptor for LTB4. (C) 2000 Elsevier Science B.V. All rights reserved.

引用

页码：51 / 58

页数：8

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