Arachidonic acid activates phospholipase D in human neutrophils;: essential role of endogenous leukotriene B4 and inhibition by adenosine A2A receptor engagement
Arachidonic acid activates phospholipase D in human neutrophils;: essential role of endogenous leukotriene B4 and inhibition by adenosine A2A receptor engagement
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DOI：
10.1189/jlb.0702371
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发表时间：
2003-04-01
影响因子：
5.5
通讯作者：
Bourgoin, SG
中科院分区：
文献类型：
--
作者：
Grenier, S;Flamand, N;Bourgoin, SG
我们在人中性粒细胞 (PMN) 中报告，微摩尔浓度的花生四烯酸 (AA) 和纳摩尔浓度的白三烯 B-4 (LTB4) 会刺激 pbospbolipase D (PLD)，而二十碳五烯酸则无活性。仅当从 PMN 悬浮液中消除腺苷或将 PMN 与腺苷 A(2A) 受体拮抗剂一起孵育时，AA 才会产生刺激作用。研究了AA诱导PLD激活的机制。结果表明，LTB4 受体 1 (BLTR1) 拮抗剂 CP 105,696 抑制 AA 和 LTB4 诱导的 PLD 激活，而 LTA(4) 水解酶抑制剂 SC57461A 和 LT 生物合成抑制剂 MK-0591 抑制 AA 介导的 PLD 激活，但不抑制 LTB4 介导的 PLD 激活。 AA 诱导的 ARF1 和 RhoA 易位至 PMN 膜可被 CP 105,696 和 SC57461A 抑制。这些结果提供了证据，表明在小 GTP 酶易位至膜以及 AA 激活 PMN PLD 中需要涉及 LTB4 和 BLTR1 的自分泌刺激环路。 J.洛科克。生物。 73：530-539； 2003年。
We report in human neutrophils (PMN) that pbospbolipase D (PLD) was stimulated by micromolar concentrations of arachidonic acid (AA) and nanomolar concentrations of leukotriene B-4 (LTB4), and eicosapentaenoic acid was inactive. The stimulatory effect of AA occurred only when adenosine was eliminated from PMN suspensions or when PMN were incubated with adenosine A(2A) receptor antagonists. The mechanism of AA-induced PLD activation was investigated. The results show that AA- and LTB4-induced PLD activation were inhibited by the LTB4 receptor 1 (BLTR1) antagonist CP 105,696, whereas the LTA(4) hydrolase inhibitor SC57461A and the LT biosynthesis inhibitor MK-0591 inhibited AA- but not LTB4- mediated PLD activation. The AA-induced ARF1 and RhoA translocation to PMN membranes was inhibited by CP 105,696 and SC57461A. These results provide evidence of a requirement for an autocrine-stimulatory loop involving LTB4 and BLTR1 in the translocation of small GTPases to membranes and the activation of PMN PLD by AA. J. Leukoc. Biol. 73: 530-539; 2003.