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PECAM‐1 engagement counteracts ICAM‐1‐induced signaling in brain vascular endothelial cells 2
Author(s) -
Couty JeanPierre,
Rampon Christine,
Leveque Mathilde,
LaranChich MariePierre,
Bourdoulous Sandrine,
Greenwood John,
Couraud PierreOlivier
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04782.x
Subject(s) - microbiology and biotechnology , icam 1 , endothelial stem cell , biology , endothelium , signal transduction , phosphorylation , tyrosine phosphorylation , actin cytoskeleton , cytoskeleton , cell adhesion molecule , cell adhesion , cell , biochemistry , endocrinology , in vitro
Interactions between leukocytes and vascular endothelial cells are mediated by a complex set of membrane adhesion molecules which transduce bi‐directional signals in both cell types. Endothelium of the cerebral blood vessels, which constitute the blood–brain barrier, strictly controls adhesion and trafficking of leukocytes into the brain. Investigating signaling pathways triggered by the engagement of adhesion molecules expressed on brain endothelial cells, we previously documented the role of ICAM‐1 in activation of the tyrosine phosphorylation of several actin‐binding proteins and subsequent rearrangements of the actin cytoskeleton. In the present study, we show that, whereas PECAM‐1 is known to control positively the trans‐endothelial migration of leukocytes via homophilic interactions between leukocytes and endothelial cells, PECAM‐1 engagement on brain endothelial surface unexpectedly counteracts the ICAM‐1‐induced tyrosine phosphorylation of cortactin and rearrangements of the actin cytoskeleton. We present evidence that the PECAM‐1‐associated tyrosine phosphatase SHP‐2 is required for ICAM‐1 signaling, suggesting that its activity might crucially contribute to the regulation of ICAM‐1 signaling by PECAM‐1. Our findings reveal a novel activity for PECAM‐1 which, by counteracting ICAM‐1‐induced activation, could directly contribute to limit activation and maintain integrity of brain vascular endothelium.