- 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.
MetadatenAuthor: | 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): | Creative Commons - Namensnennung 3.0 |
---|