β1-Integrin/Matrix Interactions Support Blood–Brain Barrier Integrity
Autor: | Britta Engelhardt |
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Rok vydání: | 2011 |
Předmět: |
Endothelium
Matrix (biology) Biology Blood–brain barrier Antibodies Tight Junctions Capillary Permeability Extracellular matrix Mice 03 medical and health sciences 0302 clinical medicine Cell Adhesion medicine Animals Claudin-5 Cells Cultured 030304 developmental biology 0303 health sciences Tight junction Integrin beta1 Feature Article β1 integrin Membrane Proteins Adhesion Corpus Striatum Extracellular Matrix Cell biology medicine.anatomical_structure Gene Expression Regulation nervous system Neurology Membrane protein cardiovascular system Neurology (clinical) Cardiology and Cardiovascular Medicine Feature Article Commentary 030217 neurology & neurosurgery |
Zdroj: | Journal of cerebral blood flow and metabolism : official journal of the International Society of Cer |
ISSN: | 1559-7016 0271-678X |
DOI: | 10.1038/jcbfm.2011.98 |
Popis: | 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. |
Databáze: | OpenAIRE |
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