Interendothelial claudin-5 expression depends on cerebral endothelial cell-matrix adhesion by Β 1-integrins

Takashi Osada, Yu Huan Gu, Masato Kanazawa, Yoshiaki Tsubota, Brian T. Hawkins, Maria Spatz, Richard Milner, Gregory J. Del Zoppo

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1972-1985
Number of pages14
JournalJournal of Cerebral Blood Flow and Metabolism
Volume31
Issue number10
DOIs
Publication statusPublished - 2011 Oct

Keywords

  • cerebral endothelial cells
  • extracellular matrix
  • laudin-5
  • matrix adhesion receptors
  • microvessel permeability
  • β1-integrins

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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    Osada, T., Gu, Y. H., Kanazawa, M., Tsubota, Y., Hawkins, B. T., Spatz, M., Milner, R., & Del Zoppo, G. J. (2011). Interendothelial claudin-5 expression depends on cerebral endothelial cell-matrix adhesion by Β 1-integrins. Journal of Cerebral Blood Flow and Metabolism, 31(10), 1972-1985. https://doi.org/10.1038/jcbfm.2011.99