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

Hiam Abdala-Valencia, Timothy S. Kountz, Michelle E. Marchese, Joan M. Cook-Mills*

*Corresponding author for this work

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

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, PKCα, and PTP1B. Furthermore, exogenous addition of the VCAM-1 signaling intermediate H 2 O 2 (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.

Original languageEnglish (US)
Pages (from-to)215-228
Number of pages14
JournalJournal of Leukocyte Biology
Volume104
Issue number1
DOIs
StatePublished - Jul 2018

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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