Monocytes induce reversible focal changes in vascular endothelial cadherin complex during transendothelial migration under flow.

Monocytes induce reversible focal changes in vascular endothelial cadherin complex during transendothelial migration under flow.
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DOI:
10.1083/jcb.148.1.203
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发表时间:
2000-01-10
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Luscinskas FW
Luscinskas FW
中科院分区:
其他
文献类型:
--
作者:
Allport JR;Muller WA;Luscinskas FW

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血管内皮细胞钙粘蛋白复合物(VE-钙粘蛋白、α-、β-和γ-连环蛋白和p120/p100)定位于血管内皮细胞周围的粘附连接,可能在循环血白细胞的跨内皮迁移中发挥关键作用。以前,我们已经报道,中性粒细胞粘附到人脐静脉内皮细胞(HUVEC)单层,在静态条件下,导致VE-钙粘蛋白复合物的显着损失。我们和其他人的后续研究(Moll,T.,E. Dejana和D.韦斯特韦伯1998. J. Cell Biol.140:403-407)表明,这种现象可能反映了在标本制备过程中释放的嗜中性粒细胞蛋白酶的降解。我们推测VE-钙粘蛋白复合物的某种形式的破坏可能是白细胞迁移过程中的一个生理过程。在本研究中,研究结果表明,一个特定的,局部的影响,迁移的白细胞上的VE-钙粘蛋白复合物在姜黄素激活的HUVEC单层。单核细胞和体外分化的U937细胞在生理流动条件下跨内皮迁移期间诱导VE-钙粘蛋白、α-连环蛋白、β-连环蛋白和斑珠蛋白染色的局灶性丢失。这些事件被阻止跨内皮迁移的抗体抑制,并在迁移后逆转。总之,这些数据表明,内皮依赖性步骤的短暂性和局灶性破坏的VE-钙粘蛋白复合物发生在白细胞迁移。
The vascular endothelial cell cadherin complex (VE-cadherin, α-, β-, and γ-catenin, and p120/p100) localizes to adherens junctions surrounding vascular endothelial cells and may play a critical role in the transendothelial migration of circulating blood leukocytes. Previously, we have reported that neutrophil adhesion to human umbilical vein endothelial cell (HUVEC) monolayers, under static conditions, results in a dramatic loss of the VE-cadherin complex. Subsequent studies by us and others (Moll, T., E. Dejana, and D. Vestweber. 1998. J. Cell Biol. 140:403–407) suggested that this phenomenon might reflect degradation by neutrophil proteases released during specimen preparation. We postulated that some form of disruption of the VE-cadherin complex might, nonetheless, be a physiological process during leukocyte transmigration. In the present study, the findings demonstrate a specific, localized effect of migrating leukocytes on the VE-cadherin complex in cytokine-activated HUVEC monolayers. Monocytes and in vitro differentiated U937 cells induce focal loss in the staining of VE-cadherin, α-catenin, β-catenin, and plakoglobin during transendothelial migration under physiological flow conditions. These events are inhibited by antibodies that prevent transendothelial migration and are reversed following transmigration. Together, these data suggest that an endothelial-dependent step of transient and focal disruption of the VE-cadherin complex occurs during leukocyte transmigration.
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