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

Am J Physiol Lung Cell Mol Physiol. 2000 Dec;279(6):L1218-25. doi: 10.1152/ajplung.2000.279.6.L1218.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adherens Junctions / drug effects
  • Adherens Junctions / metabolism
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antigens, CD
  • Cadherins / analysis
  • Cadherins / immunology
  • Cadherins / metabolism*
  • Calcium / metabolism
  • Capillary Permeability / physiology
  • Cells, Cultured
  • Chelating Agents / pharmacology
  • Edetic Acid / pharmacology
  • Electric Impedance
  • Endothelium, Vascular / chemistry
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Epitopes / immunology
  • In Vitro Techniques
  • Iodine Radioisotopes
  • Lung / blood supply*
  • Lung / cytology
  • Lung / metabolism
  • Male
  • Mice
  • Mice, Inbred Strains
  • Organ Size
  • Perfusion
  • Serum Albumin, Bovine / pharmacokinetics


  • Antibodies, Monoclonal
  • Antigens, CD
  • Cadherins
  • Chelating Agents
  • Epitopes
  • Iodine Radioisotopes
  • cadherin 5
  • Serum Albumin, Bovine
  • Edetic Acid
  • Calcium