Alteration of endothelial cell monolayer integrity triggers resynthesis of vascular endothelium cadherin.
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.
Gulino
D
D
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. gulino@ibs.fr
Delachanal
E
E
Concord
E
E
Genoux
Y
Y
Morand
B
B
Valiron
M O
MO
Sulpice
E
E
Scaife
R
R
Alemany
M
M
Vernet
T
T
D000595:Amino Acid Sequence; D015703:Antigens, CD; D001483:Base Sequence; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D002448:Cell Adhesion; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D017931:DNA Primers; D012333:RNA, Messenger; D000099152:Cadherin 5