Enhanced endothelial barrier function by monoclonal antibody activation of vascular endothelial cadherin

Ki Sook Park, Leslayann Schecterson, Barry M. Gumbiner

Research output: Contribution to journalArticlepeer-review

Abstract

Excessive vascular permeability occurs in inflammatory disease processes. Vascular endothelial cadherin (VE-cadherin) is an adhesion protein that controls vascular permeability. We identified monoclonal antibodies (mAbs) to human VE-cadherin that activate cell adhesion and inhibit the increased permeability of endothelial cell monolayers induced by thrombin receptor activator peptide-6 (TRAP-6). Two mAbs, 8A12c and 3A5a, reduce permeability, whereas an inhibitory mAb, 2E11d, enhances permeability. Activating mAbs also reduce permeability induced by tumor necrosis factor-α (TNF-α) and vascular endothelial cell growth factor (VEGF). The activating mAbs also stabilize the organization of the adherens junctions that are disrupted by TRAP-6, VEGF, or TNF-α. The activating mAbs act directly on the adhesive function of VE-cadherin because they did not block the accumulation of actin filaments stimulated by TRAP-6 and enhance physical cell-cell adhesion of VE-cadherin-expressing tissue culture cells. Therefore, VE-cadherin function can be regulated at the cell surface to control endothelial permeability.

Original languageEnglish
Pages (from-to)H1403-H1410
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume320
Issue number4
DOIs
Publication statusPublished - Apr 2021

Keywords

  • Cell junctions
  • Endothelial
  • Monoclonal antibodies
  • Permeability
  • VE-cadherin

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