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Evaluation of soluble junctional adhesion molecule-a as a biomarker of human brain endothelial barrier breakdown

Najbauer, Joseph; Haarmann, Axel; Deiß, Annika; Prochaska, Jürgen; Foerch, Christian; Weksler, Babette; Romero, Ignacio; Couraud, Pierre-Olivier; Stoll, Guido; Rieckmann, Peter and Buttmann, Mathias (2010). Evaluation of soluble junctional adhesion molecule-a as a biomarker of human brain endothelial barrier breakdown. PLoS ONE, 5(10) e13568.

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DOI (Digital Object Identifier) Link: http://dx.doi.org/10.1371/journal.pone.0013568
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Abstract

Background:
An inducible release of soluble junctional adhesion molecule-A (sJAM-A) under pro-inflammatory conditions was described in cultured non-CNS endothelial cells (EC) and increased sJAM-A serum levels were found to indicate inflammation in non-CNS vascular beds. Here we studied the regulation of JAM-A expression in cultured brain EC and evaluated sJAM-A as a serum biomarker of blood-brain barrier (BBB) function.

Methodology/Principal Findings:
As previously reported in non-CNS EC types, pro-inflammatory stimulation of primary or immortalized (hCMEC/D3) human brain microvascular EC (HBMEC) induced a redistribution of cell-bound JAM-A on the cell surface away from tight junctions, along with a dissociation from the cytoskeleton. This was paralleled by reduced immunocytochemical staining of occludin and zonula occludens-1 as well as by increased paracellular permeability for dextran 3000. Both a self-developed ELISA test and Western blot analysis detected a constitutive sJAM-A release by HBMEC into culture supernatants, which importantly was unaffected by pro-inflammatory or hypoxia/reoxygenation challenge. Accordingly, serum levels of sJAM-A were unaltered in 14 patients with clinically active multiple sclerosis compared to 45 stable patients and remained unchanged in 13 patients with acute ischemic non-small vessel stroke over time.

Conclusion:
Soluble JAM-A was not suited as a biomarker of BBB breakdown in our hands. The unexpected non-inducibility of sJAM-A release at the human BBB might contribute to a particular resistance of brain EC to inflammatory stimuli, protecting the CNS compartment.

Item Type: Journal Article
Copyright Holders: 2010 Haarmann et al.
ISSN: 1932-6203
Project Funding Details:
Funded Project NameProject IDFunding Body
Not SetNot SetTeva/Sanofi-Aventis
Not SetNot SetDeutsche Forschungsgemeinschaft (SFB 688, Teilprojekt A6)
Not SetNot Setthe State of Bavaria
Academic Unit/Department: Science > Life, Health and Chemical Sciences
Interdisciplinary Research Centre: Biomedical Research Network (BRN)
Item ID: 25922
Depositing User: Astrid Peterkin
Date Deposited: 05 Jan 2011 12:54
Last Modified: 14 Mar 2014 14:12
URI: http://oro.open.ac.uk/id/eprint/25922
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