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.
Full text available as:
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 |
| Funders: |
Teva/Sanofi-Aventis, Deutsche Forschungsgemeinschaft (SFB 688, Teilprojekt A6), the State of Bavaria |
| Academic Unit/Department: |
Science > Life, Health and Chemical Sciences |
| Item ID: |
25922 |
| Depositing User: |
Astrid Peterkin
|
| Date Deposited: |
05 Jan 2011 12:54 |
| Last Modified: |
15 Nov 2012 17:49 |
| URI: |
http://oro.open.ac.uk/id/eprint/25922 |
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