Interendothelial claudin-5 expression depends on cerebral endothelial cell-matrix adhesion by β(1)-integrins

J Cereb Blood Flow Metab. 2011 Oct;31(10):1972-85. doi: 10.1038/jcbfm.2011.99. Epub 2011 Jul 20.


The hypothesis tested by these studies states that in addition to interendothelial cell tight junction proteins, matrix adhesion by β(1)-integrin receptors expressed by endothelial cells have an important role in maintaining the cerebral microvessel permeability barrier. Primary brain endothelial cells from C57 BL/6 mice were incubated with β(1)-integrin function-blocking antibody (Ha2/5) or isotype control and the impacts on claudin-5 expression and microvessel permeability were quantified. Both flow cytometry and immunofluorescence studies demonstrated that the interendothelial claudin-5 expression by confluent endothelial cells was significantly decreased in a time-dependent manner by Ha2/5 exposure relative to isotype. Furthermore, to assess the barrier properties, transendothelial electrical resistance and permeability measurements of the monolayer, and stereotaxic injection into the striatum of mice were performed. Ha2/5 incubation reduced the resistance of endothelial cell monolayers significantly, and significantly increased permeability to 40 and 150 kDa dextrans. Ha2/5 injection into mouse striatum produced significantly greater IgG extravasation than the isotype or the control injections. This study demonstrates that blockade of β(1)-integrin function changes interendothelial claudin-5 expression and increases microvessel permeability. Hence, endothelial cell-matrix interactions via β(1)-integrin directly affect interendothelial cell tight junction claudin-5 expression and brain microvascular permeability.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Capillary Permeability / drug effects
  • Capillary Permeability / physiology
  • Cell Adhesion / physiology
  • Cells, Cultured
  • Claudin-5
  • Corpus Striatum / blood supply
  • Corpus Striatum / metabolism
  • Endothelium / cytology
  • Endothelium / metabolism*
  • Extracellular Matrix / metabolism*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Integrin beta1 / metabolism*
  • Membrane Proteins / biosynthesis*
  • Mice
  • Tight Junctions / metabolism*


  • Antibodies
  • Claudin-5
  • Cldn5 protein, mouse
  • Integrin beta1
  • Membrane Proteins