ALTERATION OF ENDOTHELIAL-CELL MONOLAYER INTEGRITY TRIGGERS RESYNTHESIS OF VASCULAR ENDOTHELIUM CADHERIN

Although cadherins appear to be necessary for proper cell-cell contact s, the physiological role of VE-cadherin (vascular endothelium cadheri n) in adult tissue has not been clearly determined. To shed some light on this question, we have disturbed the adhesive function of VE-cadhe rin in human endothelial cell culture using a polyclonal anti-VE cadhe rin antibody. This antibody disrupts confluent endothelial cell monola yers in vitro and transiently generates numerous gaps at cell-cell jun ctions. The formation of these gaps correlates with a reversible incre ase in the monolayer permeability. We present evidence that destructio n of the homotypic interactions between the extracellular domains of V E-cadherin induces a rapid resynthesis of VE-cadherin, leading to rest oration of endothelial cell-cell contacts. The expression of new molec ules of VE-cadherin correlates with a modest but significant increase in VE-cadherin mRNA synthesis, Altogether, these results establish a c ritical role for VE-cadherin in the maintenance and restoration of end othelium integrity.