title: Reversibility of increased microvessel permeability in response to VE-cadherin disassembly.
abstract: 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(2+) chelator, added to study the VE-cadherin junctional disassembly. We then repleted the perfusate with Ca(2+) to restore VE-cadherin integrity. Confocal microscopy showed a disappearance of VE-cadherin immunostaining in a time- and dose-dependent manner after Ca(2+) chelation and reassembly of the VE-cadherin complex within 5 min after Ca(2+) repletion. We determined the (125)I-labeled albumin permeability-surface area product and capillary filtration coefficient (K(fc)) to quantify alterations in the pulmonary microvessel barrier. The addition of EDTA increased (125)I-albumin permeability-surface area product and K(fc) in a concentration-dependent manner within 5 min. The permeability response was reversed within 5 min after repletion of Ca(2+). An anti-VE-cadherin monoclonal antibody against epitopes responsible for homotypic adhesion augmented the increase in K(fc) induced by Ca(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.
authors.affiliation: Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois 60612, USA.
authors.forename: X
authors.initials: X
authors.lastname: Gao
authors.forename: P
authors.initials: P
authors.lastname: Kouklis
authors.forename: N
authors.initials: N
authors.lastname: Xu
authors.forename: R D
authors.initials: RD
authors.lastname: Minshall
authors.forename: R
authors.initials: R
authors.lastname: Sandoval
authors.forename: S M
authors.initials: SM
authors.lastname: Vogel
authors.forename: A B
authors.initials: AB
authors.lastname: Malik
mesh_terms: D022005:Adherens Junctions / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD; D015820:Cadherins / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002199:Capillary Permeability / Q000502:physiology; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D017097:Electric Impedance; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D000939:Epitopes / Q000276:immunology; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008168:Lung / Q000098:blood supply* / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size; D010477:Perfusion; D012710:Serum Albumin, Bovine / Q000493:pharmacokinetics; D000099152:Cadherin 5
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015820:Cadherins; D002118:Calcium; D002614:Chelating Agents; D004492:Edetic Acid; D000939:Epitopes; D007457:Iodine Radioisotopes; D012710:Serum Albumin, Bovine; D000099152:Cadherin 5