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

81 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 1
Externally publishedYes

Fingerprint

Claudin-5
Cell-Matrix Junctions
Integrins
Permeability
Endothelial Cells
Microvessels
Intercellular Junctions
Injections
Tight Junction Proteins
Blocking Antibodies
Tight Junctions
Brain
Capillary Permeability
Dextrans
Electric Impedance
Cell Communication
Fluorescent Antibody Technique
Flow Cytometry
Immunoglobulin G

Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Osada, T., Gu, Y. H., Kanazawa, M., Tsubota, Y., Hawkins, B. T., Spatz, M., ... 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

Interendothelial claudin-5 expression depends on cerebral endothelial cell-matrix adhesion by Β 1-integrins. / Osada, Takashi; Gu, Yu Huan; Kanazawa, Masato; Tsubota, Yoshiaki; Hawkins, Brian T.; Spatz, Maria; Milner, Richard; Del Zoppo, Gregory J.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 31, No. 10, 01.10.2011, p. 1972-1985.

Research output: Contribution to journalArticle

Osada, T, Gu, YH, Kanazawa, M, Tsubota, Y, Hawkins, BT, Spatz, M, Milner, R & Del Zoppo, GJ 2011, 'Interendothelial claudin-5 expression depends on cerebral endothelial cell-matrix adhesion by Β 1-integrins', Journal of Cerebral Blood Flow and Metabolism, vol. 31, no. 10, pp. 1972-1985. https://doi.org/10.1038/jcbfm.2011.99
Osada, Takashi ; Gu, Yu Huan ; Kanazawa, Masato ; Tsubota, Yoshiaki ; Hawkins, Brian T. ; Spatz, Maria ; Milner, Richard ; Del Zoppo, Gregory J. / Interendothelial claudin-5 expression depends on cerebral endothelial cell-matrix adhesion by Β 1-integrins. In: Journal of Cerebral Blood Flow and Metabolism. 2011 ; Vol. 31, No. 10. pp. 1972-1985.
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