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PECAM-1 engagement counteracts ICAM-1-induced signaling in brain vascular endothelial cells

Couty, J.-P.; Rampon, C.; Leveque, M.; Laran-Chich, M.-P.; Bourdoulous, S.; Greenwood, J.; Couraud, P.-O.; (2007) PECAM-1 engagement counteracts ICAM-1-induced signaling in brain vascular endothelial cells. Journal of Neurochemistry , 103 (2) pp. 793-801. 10.1111/j.1471-4159.2007.04782.x. Green open access

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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.

Type: Article
Title: PECAM-1 engagement counteracts ICAM-1-induced signaling in brain vascular endothelial cells
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/j.1471-4159.2007.04782.x
Publisher version: http://dx.doi.org/10.1111/j.1471-4159.2007.04782.x
Language: English
Additional information: © 2007 The Authors. Article reproduced here in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation, for information please see http://creativecommons.org/licenses/by/2.5/
Keywords: Adhesion molecules, endothelial cells, ICAM-1, PECAM-1, signaling pathways
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/20119
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