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

Gao, Xiaopei, Panos Kouklis, Ning Xu, Richard D. Minshall, Raudel Sandoval, Stephen M. Vogel and Asrar B. Malik. Reversibility of increased microvessel permeability in response to VE-cadherin disassembly. Am J Physiol Lung Cell Mol Physiol 279: L1218-L1225, 2000.--We determined the role of vascular endothelial (VE)-cadherin complex in regulating the permeability of pulmonary microvessels. Studies were made in mouse lungs perfused with albumin-Krebs containing EDTA, a [Ca.sup.2+] chelator, added to study the VE-cadherin junctional disassembly. We then repleted the perfusate with [Ca.sup.2+] to restore VE-cadherin integrity. Confocal microscopy showed a disappearance of VE-cadherin immunostaining in a time- and dose-dependent manner after [Ca.sup.2+] chelation and reassembly of the VE-cadherin complex within 5 min after [Ca.sup.2+] repletion. We determined the [sup.125]I-labeled albumin permeability-surface area product and capillary filtration coefficient ([K.sub.fc]) to quantify alterations in the pulmonary microvessel barrier. The addition of EDTA increased [sup.125]I-albumin permeability-surface area product and [K.sub.fc] in a concentration-dependent manner within 5 min. The permeability response was reversed within 5 min after repletion of [Ca.sup.2+]. All anti-VE-cadherin monoclonal antibody against epitopes responsible for homotypic adhesion augmented the increase in [K.sub.fc] induced by [Ca.sup.2+] chelation and prevented reversal of the response. We conclude that the disassembled VE-cadherins in endothelial cells are mobilized at the junctional plasmalemmal membrane such that VE-cadherins can rapidly form adhesive contact and restore microvessel permeability by reannealing the adherens junctions. vascular endothelial-cadherin; homotypic adhesion; vascular permeability; ethylenediaminetetraacetic acid; isolated lungs; mouse