Vascular endothelial–cadherin is an important determinant of microvascular integrity invivo

Vascular endothelial–cadherin is an important determinant of microvascular integrity invivo

^*Istituto di Ricerche Farmacologiche Mario Negri, 20157 Milan, Italy; ^‖Università degli Studi dell’Insubria, Dipartimento di Scienze Cliniche e Biologiche, Facoltà di Medicina e Chirurgia, 21100 Varese, Italy; ^†Department of Anatomy and Cardiovascular Research Institute, University of California, San Francisco, CA 94143; ^‡Department of Pathology, University of Michigan, Ann Arbor, MI 48109; ^§F. Hoffmann–La Roche AG, CH4070 Basel, Switzerland; and ^¶Università degli Studi La Sapienza, Dipartimento di Medicina Sperimentale e Patologia, 00161 Rome, Italy

Edited by George E. Palade, University of California at San Diego, La Jolla, CA, and approved April 13, 1999 (received for review November 18, 1998)

Abstract

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.

Footnotes

↵ ** To whom reprint requests should be addressed at: Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea 62, 20157 Milan, Italy. E-mail: Dejana{at}irfmn.mnegri.it.
This paper was submitted directly (Track II) to the Proceedings Office.
ABBREVIATIONS:

VE,

vascular endothelial;

PECAM,

platelet endothelial cell adhesion molecule;

ZO-1,

zonula occludens 1;

JAM,

junctional adhesion molecule;

TJ,

tight junction;

AJ,

adherens junction