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.

中文翻译：

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单克隆抗体激活血管内皮钙粘蛋白增强内皮屏障功能

过度的血管通透性发生在炎症性疾病过程中。血管内皮钙粘蛋白 (VE-cadherin) 是一种控制血管通透性的粘附蛋白。我们鉴定了针对人 VE-钙粘蛋白的单克隆抗体 (mAb)，它们可激活细胞粘附并抑制由凝血酶受体激活肽-6 (TRAP-6) 诱导的内皮细胞单层通透性增加。两种 mAb 8A12c 和 3A5a 可降低渗透性，而抑制性 mAb 2E11d 可增强渗透性。激活 mAb 还可降低由肿瘤坏死因子-α (TNF-α) 和血管内皮细胞生长因子 (VEGF) 诱导的通透性。活化 mAb 还稳定被 TRAP-6、VEGF 或 TNF-α 破坏的粘附连接的组织。活化 mAb 直接作用于 VE-cadherin 的粘附功能，因为它们不会阻止受 TRAP-6 刺激的肌动蛋白丝的积累，并增强表达 VE-cadherin 的组织培养细胞的物理细胞-细胞粘附。因此，可以在细胞表面调节VE-钙粘蛋白功能以控制内皮通透性。