Interendothelial claudin-5 expression depends on cerebral endothelial cell-matrix adhesion by [beta]1-integrins

• Published in: Journal of cerebral blood flow and metabolism Vol. 31; no. 10; p. 1972
• Main Authors: Osada, Takashi, Gu, Yu-huan, Kanazawa, Masato, Tsubota, Yoshiaki, Hawkins, Brian T, Spatz, Maria, Milner, Richard, Del Zoppo, Gregory J
• Format: Journal Article
• Language: English
• Published: London Sage Publications Ltd 01.10.2011
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1038/jcbfm.2011.99

The hypothesis tested by these studies states that in addition to interendothelial cell tight junction proteins, matrix adhesion by [beta](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 [beta](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 [beta](1)-integrin function changes interendothelial claudin-5 expression and increases microvessel permeability. Hence, endothelial cell-matrix interactions via [beta](1)-integrin directly affect interendothelial cell tight junction claudin-5 expression and brain microvascular permeability.