Histamine induces tyrosine phosphorylation of endothelial cell-to-cell adherens junctions
Histamine induces tyrosine phosphorylation of endothelial cell-to-cell adherens junctions
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DOI：
10.1161/01.atv.19.10.2286
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发表时间：
1999-10-01
影响因子：
8.7
通讯作者：
Dejana, E
中科院分区：
文献类型：
--
作者：
Andriopoulou, P;Navarro, P;Dejana, E
内皮粘附连接（AJ）促进细胞间粘附，并可能有助于控制血管通透性。这些结构由跨膜和细胞特异性粘附蛋白形成，即血管内皮（VE）-钙粘蛋白，其通过其胞质尾与称为连环蛋白（α-连环蛋白、β-连环蛋白和斑珠蛋白）的细胞内蛋白和肌动蛋白细胞骨架连接。关于AJ在内皮细胞中的功能调节知之甚少。在这项研究中，我们分析了组胺对培养的内皮细胞AJ组织的影响。我们首先观察到，组胺诱导可检测到的细胞间间隙，仅在松散融合的细胞，而这种影响是强烈减少或缺乏长融合文化。尽管有这种差异，在体外渗透性增加组胺在这两种条件下。在静息状态下，AJ组分的酪氨酸磷酸化和渗透性值在最近汇合的细胞中高于长汇合的细胞。组胺没有影响AJ的磷酸化状态，在最近汇合的细胞，但强烈增加这个参数在长汇合的文化。此外，在长汇合的细胞，组胺引起的VE-钙粘蛋白从肌动蛋白细胞骨架的解离测量的细胞提取物的洗涤剂不溶性部分中的分子的量的减少。二丁酰cAMP能够阻止组胺对AJ组分的酪氨酸磷酸化和对内皮通透性的影响。组胺对VE-钙粘蛋白的作用是特异性的，因为神经（N）-钙粘蛋白（另一种主要的内皮钙粘蛋白）的磷酸化状态不受该药物的影响。因此，AJ组件是组胺激活级联反应的目标，我们认为，诱导VE-钙粘蛋白和连环蛋白的酪氨酸磷酸化有助于组胺对渗透性的影响，即使在没有坦率的细胞间间隙和细胞收缩。
Endothelial adherens junctions (AJ) promote intercellular adhesion and may contribute to the control of vascular permeability. These structures are formed by a transmembrane and cell-specific adhesive protein, vascular endothelial (VE)-cadherin, which is linked by its cytoplasmic tail to intracellular proteins called catenins (alpha-catenin, beta-catenin, and plakoglobin) and to the actin cytoskeleton. Little is known about the functional regulation of AJ in endothelial cells. In this study, we analyzed the effect of histamine on AJ organization in cultured endothelial cells. We first observed that histamine induced detectable intercellular gaps only in loosely-confluent cells, whereas this effect was strongly reduced or absent in long-confluent cultures. Despite this difference, in vitro permeability was augmented by histamine in both conditions. In resting conditions, tyrosine phosphorylation of AJ components and permeability values were higher in recently-confluent cells as compared with long-confluent cells. Histamine did not affect the phosphorylation state of AJ in recently-confluent cells but strongly increased this parameter in long-confluent cultures. In addition, in long-confluent cells, histamine caused dissociation of VE-cadherin from the actin cytoskeleton measured by a decrease of the amount of the molecule in the detergent-insoluble fraction of the cell extracts. Dibutyryl cAMP was able to prevent the effect of histamine on both tyrosine phosphorylation of AJ components and on endothelial permeability. The effect of histamine was specific for VE-cadherin because the phosphorylation slate of neural (N)-cadherin, the other major endothelial cadherin, was unchanged by this agent. Hence AJ components are a target of histamine activation cascade; we suggest that induction of tyrosine phosphorylation of VE-cadherin and catenins contributes to the histamine effect on permeability, even in absence of frank intercellular gaps and cell retraction.