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

Enhanced endothelial barrier function by monoclonal antibody activation of vascular endothelial cadherin.
Am J Physiol Heart Circ Physiol. 2021 Feb 12;:
Authors: Park KS, Schecterson L, Gumbiner BM
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 while 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.
PMID: 33577432 [PubMed - as supplied by publisher]

Source: American Journal of Physiology. Heart and Circulatory Physiology - February 12, 2021 Category: Physiology Authors: Park KS, Schecterson L, Gumbiner BM Tags: Am J Physiol Heart Circ Physiol Source Type: research