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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Osada, T; Gu, Y-H; Kanazawa, M; Tsubota, Y; Hawkins, BT; Spatz, M; Milner, R; del Zoppo, GJ

Published Date

  • October 2011

Published In

Volume / Issue

  • 31 / 10

Start / End Page

  • 1972 - 1985

PubMed ID

  • 21772312

Pubmed Central ID

  • PMC3208159

Electronic International Standard Serial Number (EISSN)

  • 1559-7016

International Standard Serial Number (ISSN)

  • 0271-678X

Digital Object Identifier (DOI)

  • 10.1038/jcbfm.2011.99

Language

  • eng