Evaluation of soluble junctional adhesion molecule-A as a biomarker of human brain endothelial barrier breakdown
2010
Online
academicJournal
Zugriff:
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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Evaluation of soluble junctional adhesion molecule-A as a biomarker of human brain endothelial barrier breakdown
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Autor/in / Beteiligte Person: | Haarmann, Axel ; Deiß, Annika ; Prochaska, Jürgen ; Förch, Christian ; Weksler, Babette ; Romero, Ignacio ; Couraud, Pierre-Olivier ; Stoll, Guido ; Rieckmann, Peter ; Buttmann, Mathias |
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Veröffentlichung: | 2010 |
Medientyp: | academicJournal |
DOI: | 10.1371/journal.pone.0013568 |
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