Commonly used leukotriene B4 receptor antagonists possess intrinsic activity as agonists in human endothelial cells: Effects on calcium transients, adhesive events and mediator release
Commonly used leukotriene B4 receptor antagonists possess intrinsic activity as agonists in human endothelial cells: Effects on calcium transients, adhesive events and mediator release
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DOI：
10.1016/j.plefa.2010.11.003
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发表时间：
2011-03-01
影响因子：
3
通讯作者：
Palmblad, Jan
中科院分区：
文献类型：
--
作者：
Johansson, Anne-Sofie;Haeggstrom, Jesper Z.;Palmblad, Jan
白三烯 B4 (LTB4) 是一种有效的趋化和免疫调节脂质介质，通过 BLT1 和 BLT2 两种受体发出信号，导致吞噬细胞产生促炎反应。最近，我们报道 BLT1 是人脐静脉内皮细胞 (HUVEC) 上的主要 BLT，并传递多种功能反应。在这里，我们证明，在 HUVEC 中，两种 BLT1 拮抗剂（U75302、CP105696）和一种 BLT2 拮抗剂（LY255283）对中性粒细胞粘附、E-选择素、ICAM-1 和 VCAM-1 上调以及 MCP-1 释放具有内在但不同的激动剂活性。这些效应在 HUVEC 暴露于药物 0.25-6 小时后观察到，持续数小时，并且强度不如 LPS 引起的效应强。我们的研究结果可能会对体外 BLT 阻断实验的解释产生影响。 (C) 2010 Elsevier Ltd. 保留所有权利。
Leukotriene B4 (LTB4), a potent chemotactic and immune-modulating lipid mediator, signals via two receptors, BLT1 and BLT2, leading to pro-inflammatory responses in phagocytes. Recently, we reported that BLT1 is the predominating BLT on human umbilical vein endothelial cells (HUVEC) and transmits a variety of functional responses. Here, we demonstrate that, in HUVEC, two BLT1 antagonists (U75302, CP105696) and one BLT2 antagonist (LY255283) possess intrinsic but varying agonist activity for adhesion of neutrophils, up-regulation of E-selectin, ICAM-1 and VCAM-1, and release of MCP-1. These effects were observed after exposure of HUVEC for the drugs for 0.25-6 h, persisted for several hours, and were less potent in magnitude as those elicited by LPS. Our findings may have consequences for interpretation of in vitro BLT blockade experiments. (C) 2010 Elsevier Ltd. All rights reserved.