Vascular endothelial-cadherin is an important determinant of microvascular integrity in vivo

Vascular endothelial-cadherin is an important determinant of microvascular integrity in vivo
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DOI:
10.1073/pnas.96.17.9815
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发表时间:
1999-08-17
影响因子:
11.1
通讯作者:
Dejana, E
Dejana, E
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Corada, M;Mariotti, M;Dejana, E

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在本文中,我们描述了一种针对小鼠血管内皮(VE)-钙粘蛋白(内皮间粘附连接的主要粘附蛋白)的抗体mAb BV 13。当加入到培养的内皮细胞中时,BV 13诱导VE-钙粘蛋白从细胞间连接处重新分布。VE-钙粘蛋白再分布并不改变血小板内皮细胞粘附分子或紧密连接标记物(如闭锁小带1、扣带蛋白和连接粘附分子)的定位。静脉内给予mAb BV 13诱导心脏和肺中血管通透性的浓度和时间依赖性增加。电镜下可见心、肺间质水肿及混合型炎性细胞聚集。注射(罗丹明标记)蓖麻凝集素I显示肺泡毛细血管和一些较大的肺血管中暴露的基底膜的焦点。这些数据表明,VE-钙粘蛋白是血管完整性和正常器官功能所必需的。
In the present paper, we characterize an antibody, mAb BV13, directed to mouse vascular endothelial (VE)-cadherin, a major adhesive protein of interendothelial adherens junctions. When added to cultured endothelial cells, BV13 induces a redistribution of VE-cadherin from intercellular junctions. VE-cadherin redistribution did not change the localization of platelet endothelial cell adhesion molecule or tight junction markers such as zonula occludens 1, cingulin, and junctional adhesion molecule. Intravenous administration of mAb BV13 induced a concentration- and time-dependent increase in vascular permeability in heart and lungs. By electron microscopy, interstitial edema and accumulation of mixed types of inflammatory cells in heart and lungs were observed. Injection of (rhodamine-labeled) Ricinus communis I lectin showed focal spots of exposed basement membrane in the alveolar capillaries and in some larger pulmonary vessels. These data indicate that VE-cadherin is required for vascular integrity and normal organ functions.