Vascular Endothelial-Cadherin Is an Important Determinant of Microvascular Integrity in vivo

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 96; no. 17; pp. 9815 - 9820
• Main Authors: Corada, Monica, Mariotti, Massimo, Thurston, Gavin, Smith, Kelly, Kunkel, Robin, Brockhaus, Manfred, Lampugnani, Maria Grazia, Martin-Padura, Ines, Stoppacciaro, Antonella, Ruco, Luigi, McDonald, Donald M., Ward, Peter A., Dejana, Elisabetta
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 17.08.1999; National Academy of Sciences; The National Academy of Sciences
• Subjects: Animals; Antibodies; Antibodies, Monoclonal; Antigens, CD; Basement membrane; Biological Sciences; Cadherins - immunology; Cadherins - physiology; Capillaries; Capillary Permeability; Cells; Cells, Cultured; Complement Activation; Endothelial cells; Endothelium, Vascular - physiology; Epithelial cells; Heart; Lungs; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Nude; Microcirculation - physiology; Neutrophils; Pathology; Platelets; Proteins; Pulmonary alveoli; Rats; Rats, Inbred Lew; Ricin
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.96.17.9815

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.