Vascular endothelial–cadherin is an important determinant of microvascular integrityinvivo

• DOI: 10.1073/pnas.96.17.9815
• Publication Date: 2002-07-26T14:35:07Z
• Authors: Monica Corada; Massimo Mariotti; Gavin Thurston; Kelly Smith; Robin Kunkel; Manfred Brockhaus; Maria Grazia Lamp...; Ines Martin-Padura; Antonella Stoppac...; Luigi Ruco; Donald M. McDonald; Peter A. Ward; Elisabetta Dejana
• Keywords: Male; 0301 basic medicine; Mice, Inbred BALB C; Microcirculation; Antibodies, Monoclonal; Mice, Nude; Ricin; adherens junction; endothelium; permeability; Cadherins; Rats; 3. Good health; Capillary Permeability; Mice, Inbred C57BL; Mice; 03 medical and health sciences; endothelium, permeability, adherens junction, VE-cadherin; Antigens, CD; Mice, Inbred DBA; Rats, Inbred Lew; Animals; Endothelium, Vascular; Complement Activation; Cells, Cultured

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 communisI 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.