首页> 外文期刊>American Journal of Physiology >Histamine selectively interrupts VE-cadherin adhesion independently of capacitive calcium entry.
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Histamine selectively interrupts VE-cadherin adhesion independently of capacitive calcium entry.

机译:组胺选择性地中断VE-钙黏着蛋白的粘附,而与电容性钙的进入无关。

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Histamine is an important agent of innate immunity, transiently increasing the flux of immune-competent molecules from the vascular space to the tissues and then allowing rapid restoration of the integrity of the endothelial barrier. In previous work we found that histamine alters the endothelial barrier by disrupting cell-cell adhesion and identified VE-cadherin as an essential participant in this process. The previous work did not determine whether histamine directly interrupted VE-cadherin adhesion, whether the effects of histamine were selective for cadherin adhesion, or whether capacitive calcium flux across the cell membrane was necessary for the effects of histamine on cell-cell adhesion. In the current work we found that histamine directly interrupts adhesion of L cells expressing the type 1 histamine (H1) receptor and VE-cadherin to a VE-cadherin-Fc fusion protein. In contrast, integrin-mediated adhesion to fibronectin of the same L cells expressing the H1 receptor was not affected by histamine, demonstrating that the effects of histamine are selective for cadherin adhesion. Some of the effects of many edemagenic agonists on endothelium are dependent on the capacitive flux of calcium across the endothelial cell membrane. Blocking capacitive calcium flux with LaCl3 did not prevent histamine from interrupting VE-cadherin adhesion of transfected L cells, nor did it prevent histamine from interrupting cell-cell adhesion of human umbilical vein endothelial cells. These data support the contentions that histamine directly and selectively interrupts cadherin adhesion and this effect on cadherin adhesion is independent of capacitive calcium flux.
机译:组胺是先天免疫的重要物质,可暂时增加具有免疫功能的分子从血管腔到组织的通量,然后迅速恢复内皮屏障的完整性。在以前的工作中,我们发现组胺通过破坏细胞与细胞的粘附来改变内皮屏障,并确定VE-钙粘着蛋白是该过程的重要参与者。先前的工作并未确定组胺是否直接打断VE-钙粘蛋白的粘附,组胺的作用是否对钙粘蛋白粘附具有选择性,或者是否需要穿过细胞膜的电容性钙通量对于组胺对细胞与细胞粘附的作用是必需的。在当前的工作中,我们发现组胺直接中断表达1型组胺(H1)受体和VE-钙粘蛋白的L细胞与VE-钙粘蛋白-Fc融合蛋白的粘附。相反,整联蛋白介导的表达H1受体的L细胞与纤连蛋白的粘附不受组胺的影响,表明组胺对钙粘蛋白的粘附具有选择性。许多水肿激动剂对内皮的某些作用取决于钙穿过内皮细胞膜的电容通量。用LaCl3阻断电容性钙通量并不能阻止组胺干扰转染的L细胞的VE-钙黏着蛋白粘附,也不能阻止组胺干扰人脐静脉内皮细胞的细胞粘附。这些数据支持组胺直接和选择性地打断钙黏着蛋白粘附的观点,这种对钙黏着蛋白粘附的影响与电容性钙通量无关。

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