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CCL2 disrupts the adherens junction: implications for neuroinflammation

Roberts, Toni K; Eugenin, Eliseo A; Lopez, Lillie; Romero, Ignacio A; Weksler, Babette B; Couraud, Pierre-Olivier and Berman, Joan W (2012). CCL2 disrupts the adherens junction: implications for neuroinflammation. Laboratory investigation; a journal of technical methods and pathology, 92(8) pp. 1213–1233.

DOI (Digital Object Identifier) Link: http://dx.doi.org/10.1038/labinvest.2012.80
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Abstract

Alterations to blood-brain barrier (BBB) adhesion molecules and junctional integrity during neuroinflammation can promote central nervous system (CNS) pathology. The chemokine CCL2 is elevated during CNS inflammation and is associated with endothelial dysfunction. The effects of CCL2 on endothelial adherens junctions (AJs) have not been defined. We demonstrate that CCL2 transiently induces Src-dependent disruption of human brain microvascular endothelial AJ. β-Catenin is phosphorylated and traffics from the AJ to PECAM-1 (platelet endothelial cell adhesion molecule-1), where it is sequestered at the membrane. PECAM-1 is also tyrosine-phosphorylated, an event associated with recruitment of the phosphatase SHP-2 (Src homology 2 domain-containing protein phosphatase) to PECAM-1, β-catenin release from PECAM-1, and reassociation of β-catenin with the AJ. Surface localization of PECAM-1 is increased in response to CCL2. This may enable the endothelium to sustain CCL2-induced alterations in AJ and facilitate recruitment of leukocytes into the CNS. Our novel findings provide a mechanism for CCL2-mediated disruption of endothelial junctions that may contribute to BBB dysfunction and increased leukocyte recruitment in neuroinflammatory diseases.

Item Type: Journal Article
Copyright Holders: 2012 Nature Publishing Group
ISSN: 1530-0307
Keywords: β-catenin; CD31; endothelial cells; MCP-1; neuroinflammation; PECAM-1; VE-cadherin
Academic Unit/Department: Science > Life, Health and Chemical Sciences
Interdisciplinary Research Centre: Biomedical Research Network (BRN)
Related URLs:
Item ID: 34223
Depositing User: Ignacio A Romero
Date Deposited: 22 Aug 2012 09:32
Last Modified: 07 Mar 2014 15:06
URI: http://oro.open.ac.uk/id/eprint/34223
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