Oxidant stress-induced transendothelial migration of monocytes is linked to phosphorylation of PECAM-1
Oxidant stress-induced transendothelial migration of monocytes is linked to phosphorylation of PECAM-1
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DOI：
10.1152/ajpendo.1997.273.3.e453
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发表时间：
1997-09-01
影响因子：
5.1
通讯作者：
Kalra, VK
中科院分区：
文献类型：
--
作者：
Rattan, V;Sultana, C;Kalra, VK
在动脉粥样硬化、糖尿病和镰状细胞病的血管闭塞的病理生理学中，活性氧（ROS）被认为是导致血管损伤的原因。研究表明，ROS导致单核细胞和中性粒细胞与内皮细胞的粘附增加。我们研究了氧化应激诱导剂叔丁基过氧化氢（t-BuOOH）的影响，以确定导致多形核白细胞跨内皮迁移的细胞信号通路。我们的研究表明，t-BuOOH在人脐静脉内皮细胞（HUVECs）中的信号传导导致单核细胞样HL-60细胞跨内皮迁移增加2倍，血小板内皮细胞粘附分子-1（PECAM-1）磷酸化增加5倍。PECAM-1抗体可抑制t-BuOOH诱导的迁移。抗氧化剂和蛋白激酶C、p21（ras）和谷胱甘肽合成抑制剂可抑制这些事件。然而，用磷酸酶抑制剂calyculin A处理HUVECs增强了t-BuOOH介导的单核细胞跨内皮迁移和PECAM-1磷酸化。我们的研究结果表明，氧化应激可以诱导单核细胞的跨内皮迁移的PECAM-1的磷酸化，在血管疾病的病理生理过程中的白细胞渗出的一个至关重要的事件。
Reactive oxygen species (ROS) are believed to cause vascular injury in the pathophysiology of atherosclerosis, diabetes, and vasoocclusion in sickle cell disease. Studies have shown that ROS causes increased adhesion of monocytes and neutrophils to the endothelium. We investigated the effects of tert-butylhydroperoxide (t-BuOOH), an inducer of oxidant stress, to determine the cellular signaling pathway leading to the transendothelial migration of polymorphonuclear leukocytes. Our studies revealed that signaling by t-BuOOH in human umbilical vein endothelial cells (HUVECs) causes a twofold increase in the transendothelial migration of monocyte-like HL-60 cells and a fivefold increase in platelet endothelial cell adhesion molecule-1 (PECAM-1) phosphorylation. The transmigration induced by t-BuOOH was inhibited by an antibody to PECAM-1. These events were inhibited by antioxidants and inhibitors of protein kinase C, p21(ras) and glutathione synthesis. However, treatment of HUVECs with the phosphatase inhibitor calyculin A augmented the t-BuOOH-mediated transendothelial migration of monocytes and PECAM-1 phosphorylation. Our results suggest that oxidative stress can induce the transendothelial migration of monocytes as a result of phosphorylation of PECAM-1, a crucial event in the diapedesis of leukocytes during pathophysiology of vascular diseases.