VCAM-1 induces signals that stimulate ZO-1 serine phosphorylation and reduces ZO-1 localization at lung endothelial cell junctions.
VCAM-1 induces signals that stimulate ZO-1 serine phosphorylation and reduces ZO-1 localization at lung endothelial cell junctions.
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DOI：
10.1002/jlb.2ma1117-427rr
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发表时间：
2018-07
影响因子：
5.5
通讯作者：
Cook-Mills JM
中科院分区：
文献类型：
--
作者：
Abdala-Valencia H;Kountz TS;Marchese ME;Cook-Mills JM
内皮细胞血管细胞粘附分子-1（VCAM-1）调节过敏性炎症过程中淋巴细胞、嗜酸性粒细胞、肥大细胞或树突状细胞的募集。在这份报告中，我们证明，在过敏性肺反应，有减少ZO-1定位在肺内皮细胞连接，而有增加的VCAM-1，N-钙粘蛋白，血管动蛋白的肺内皮细胞表达。在体外，白细胞与VCAM-1的结合减少了内皮细胞连接中的ZO-1。使用原代人内皮细胞和小鼠内皮细胞系，VCAM-1的抗体交联增加了ZO-1的丝氨酸磷酸化并诱导ZO-1从内皮细胞连接处解离，表明VCAM-1调节ZO-1。此外，VCAM-1诱导ZO-1磷酸化和ZO-1在细胞连接处定位的丧失可通过抑制VCAM-1细胞内信号（包括NOX 2、PKCα和PTP 1B）来阻断，VCAM-1细胞内信号调节白细胞跨内皮迁移。此外，外源性添加VCAM-1信号传导中间体H2 O2（1 μM）可刺激ZO-1的PKCα依赖性和PTP 1B依赖性丝氨酸磷酸化以及连接处ZO-1的丢失。ZO-1的过表达阻断了白细胞的跨内皮迁移。总之，白细胞与VCAM-1的结合诱导了刺激ZO-1丝氨酸磷酸化的信号，并减少了白细胞跨内皮迁移过程中ZO-1在内皮细胞连接处的定位。
Endothelial cell vascular cell adhesion molecule-1 (VCAM-1) regulates recruitment of lymphocytes, eosinophils, mast cells or dendritic cells during allergic inflammation. In this report, we demonstrated that, during allergic lung responses, there was reduced ZO-1 localization in lung endothelial cell junctions, whereas there was increased lung endothelial cell expression of VCAM-1, N-Cadherin, and angiomotin. In vitro, leukocyte binding to VCAM-1 reduced ZO-1 in endothelial cell junctions. Using primary human endothelial cells and mouse endothelial cell lines, antibody crosslinking of VCAM-1 increased serine phosphorylation of ZO-1 and induced dissociation of ZO-1 from endothelial cell junctions, demonstrating that VCAM-1 regulates ZO-1. Moreover, VCAM-1 induction of ZO-1 phosphorylation and loss of ZO-1 localization at cell junctions was blocked by inhibition of VCAM-1 intracellular signals that regulate leukocyte transendothelial migration, including NOX2, PKCα, and PTP1B. Furthermore, exogenous addition of the VCAM-1 signaling intermediate H2O2 (1 μM) stimulated PKCα-dependent and PTP1B-dependent serine phosphorylation of ZO-1 and loss of ZO-1 from junctions. Overexpression of ZO-1 blocked leukocyte transendothelial migration. In summary, leukocyte binding to VCAM-1 induces signals that stimulated ZO-1 serine phosphorylation and reduced ZO-1 localization at endothelial cell junctions during leukocyte transendothelial migration.