Reversibility of increased microvessel permeability in response to VE-cadherin disassembly

We determined the role of vascular endothelial (VE)-cadherin complex in reg ulating the permeability of pulmonary microvessels. Studies were made in mo use lungs perfused with albumin-Krebs containing EDTA, a Ca2+ chelator, add ed to study the VE-cadherin junctional disassembly. We then repleted the pe rfusate with Ca2+ to restore VE-cadherin integrity. Confocal microscopy sho wed a disappearance of VE-cadherin immunostaining in a time- and dose-depen dent manner after Ca2+ chelation and reassembly of the VE-cadherin complex within 5 min after Ca2+ repletion. We determined the I-125-labeled albumin permeability-surface area product and capillary filtration coefficient (K-f c) to quantify alterations in the pulmonary microvessel barrier. The additi on of EDTA increased I-125-albumin permeability-surface area product and K- fc in a concentration-dependent manner within 5 min. The permeability respo nse was reversed within 5 min after repletion of Ca2+. An anti-VE-cadherin monoclonal antibody against epitopes responsible for homotypic adhesion aug mented the increase in K-fc induced by Ca2+ chelation and prevented reversa l of the response. We conclude that the disassembled VE-cadherins in endoth elial cells are mobilized at the junctional plasmalemmal membrane such that VE-cadherins can rapidly form adhesive contact and restore microvessel per meability by reannealing the adherens junctions.