VCAM-1 induces signals that stimulate ZO-1 serine phosphorylation and reduces ZO-1 localization at lung endothelial cell junctions

作者：Abdala Valencia Hiam; Kountz Timothy S; Marchese Michelle E; Cook Mills Joan M^*

来源：Journal of Leukocyte Biology, 2018, 104(1): 215-228.

DOI：10.1002/JLB.2MA1117-427RR

• endothelial cells
• lymphocyte migration
• VCAM-1
• ZO-1

Endothelial cell 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 zonula occludens (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, Ab 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, PKC, and PTP1B. Furthermore, exogenous addition of the VCAM-1 signaling intermediate H2O2 (1 M) stimulated PKC-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.
VCAM-1 signaling through ROS, PKCalpha, and PTP1B induce serine phosphorylation of ZO-1 and loss of ZO-1 from endothelial cell junctions during VCAM-1-dependent leukocyte transendothelial migration.

• 出版日期2018-7
• 单位西北大学