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

  • 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.

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Author:Axel Haarmann, Annika Deiß, Jürgen Prochaska, Christian FörchORCiDGND, Babette Weksler, Ignacio Romero, Pierre-Olivier Couraud, Guido Stoll, Peter Rieckmann, Mathias Buttmann
URN:urn:nbn:de:hebis:30-114434
DOI:https://doi.org/10.1371/journal.pone.0013568
ISSN:1932-6203
Parent Title (English):PLoS One
Document Type:Article
Language:English
Date of Publication (online):2010/10/21
Date of first Publication:2010/10/21
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2011/09/06
Volume:5
Issue:(10): e13568
Note:
Copyright: © 2010 Haarmann et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Source:PLoS ONE 5(10): e13568. doi: 10.1371/journal.pone.0013568
HeBIS-PPN:276033310
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Sammlung Biologie / Sondersammelgebiets-Volltexte
Licence (German):License LogoCreative Commons - Namensnennung 3.0