Alteration of Endothelial Cell Monolayer Integrity Triggers Resynthesis of Vascular Endothelium Cadherin*
- Danielle Gulino‡§,
- Elisabeth Delachanal¶,
- Evelyne Concord‡,
- Yolande Genoux¶,
- Blandine Morand‡,
- Marie-Odile Valiron¶,
- Eric Sulpice¶,
- Robin Scaife¶‖,
- Monica Alemany¶ and
- Thierry Vernet‡
- From the ¶Laboratoire d’Hématologie, Département de Biologie Moléculaire et Structurale, Commissariat àl’Energie Atomique, 17, Avenue des Martyrs, 38054 Grenoble Cedex, France and the ‡Laboratoire d’Ingénierie des Macromolécules, Institut de Biologie Structurale Jean-Pierre Ebel (Commissariat à l’Energie Atomique/CNRS), 41, Avenue des Martyrs, 38027 Grenoble Cedex, France
Abstract
Although cadherins appear to be necessary for proper cell-cell contacts, the physiological role of VE-cadherin (vascular endothelium cadherin) in adult tissue has not been clearly determined. To shed some light on this question, we have disturbed the adhesive function of VE-cadherin in human endothelial cell culture using a polyclonal anti-VE-cadherin antibody. This antibody disrupts confluent endothelial cell monolayers in vitro and transiently generates numerous gaps at cell-cell junctions. The formation of these gaps correlates with a reversible increase in the monolayer permeability. We present evidence that destruction of the homotypic interactions between the extracellular domains of VE-cadherin induces a rapid resynthesis of VE-cadherin, leading to restoration of endothelial cell-cell contacts. The expression of new molecules of VE-cadherin correlates with a modest but significant increase in VE-cadherin mRNA synthesis. Altogether, these results establish a critical role for VE-cadherin in the maintenance and restoration of endothelium integrity.
Footnotes
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↵* This work was supported by Grant 6889 from the Association pour la Recherche sur le Cancer. This is Publication 555 of the Institut de Biologie Structurale Jean-Piere Ebel.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵§ To whom correspondence should be addressed: E-mail:gulino{at}ibs.fr.
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↵‖ Present address: Dept. of Pathology, University of Western Australia, Nedlands, Perth WA 6009, Australia.
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↵2 P. Huber, personal communication.
- Abbreviations:
- CHO
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Chinese hamster ovary
- mAb
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monoclonal antibody
- MOPS
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4-morpholinepropanesulfonic acid
- GAPDH
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glyceraldehyde-3-phosphate dehydrogenase.
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- Received May 20, 1998.
- Revision received August 13, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
