Characterization of prostaglandin E2 generation through the cyclooxygenase (COX)-2 pathway in human neutrophils
Characterization of prostaglandin E2 generation through the cyclooxygenase (COX)-2 pathway in human neutrophils
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DOI：
10.1016/j.bbalip.2007.06.002
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发表时间：
2007-09-01
影响因子：
4.8
通讯作者：
Pouliot, Marc
中科院分区：
文献类型：
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作者：
St-Onge, Mireille;Flamand, Nicolas;Pouliot, Marc
在本研究中，我们的特点是产生前列腺素（PG）E-2在人类中性粒细胞。我们发现钙离子依赖的IV型胞质磷脂酶A（2）（cPLA（2））参与了考克斯-2介导的PGE（2）的生成，并对钙离子载体做出了反应，这一点通过使用选择的PLA（2）抑制剂来确定。由细菌源性肽或作用于细胞表面受体的吞噬刺激引起的PGE（2）生物合成也显示依赖于cPLA 2活性。然后，我们评估了未酯化的花生四烯酸（AA）的代谢，并观察到，PGE 2的生产变得有利于LTB 4与较高的AA浓度。撤回钙阻止生成的PGE 2响应钙离子载体，但不影响上调的考克斯-2或其能力，转换AA，从而限制其在cPLA 2激活水平的影响。在中性粒细胞产生的主要类花生酸中，只有LTB 4能够上调考克斯-2的表达。最后，中性粒细胞中发现的唯一PGE合酶亚型是微粒体PGE合酶-1;它与考克斯-2共定位，其表达主要是组成型的。这些结果强调了5-LO和考克斯途径调节过程中的关键差异，并增强了我们对中性粒细胞中PGE 2生物合成多个水平的了解。(C)2007 Elsevier B. V.保留所有权利。
In the present study, we characterized the generation of prostaglandin (PG)E-2 in human neutrophils. We found that the Ca2+-dependent type IV cytosolic phospholipase A(2) (cPLA(2)) was pivotally involved in the COX-2-mediated generation of PGE(2) in response to a calcium ionophore, as determined by the use of selected PLA(2) inhibitors. PGE(2) biosynthesis elicited by bacterial-derived pepticles or by phagocytic stimuli acting on cell surface receptors also showed to be dependent on cPLA2 activity. We then assessed metabolism of unesterified arachidonic acid (AA), and observed that PGE2 production becomes favored over that of LTB4 with higher AA concentrations. Withdrawal of calcium prevented the generation of PGE2 in response to a calcium ionophore but did not affect the up-regulation of COX-2 or its capacity to convert AA, thus limiting its implication at the level of cPLA2 activation. Of the main cicosanoids produced by neutrophils, only LTB4 was able to up-regulate COX-2 expression. Finally, the only PGE synthase isoform found in neutrophils is microsomal PGE synthase-1; it co-localized with COX-2 and its expression appeared mainly constitutive. These results highlight key differences in regulatory processes of the 5-LO and COX pathways, and enhance our knowledge at several levels in the PGE2 biosynthesis in neutrophils. (C) 2007 Elsevier B.V. All rights reserved.