Evaluation of Soluble Junctional Adhesion Molecule-A as a Biomarker of Human Brain Endothelial Barrier Breakdown
In: ftp://ftp.ncbi.nlm.nih.gov/pub/pmc/25/6d/PLoS_One_2010_Oct_21_5(10)_e13568.tar.gz
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
Titel: |
Evaluation of Soluble Junctional Adhesion Molecule-A as a Biomarker of Human Brain Endothelial Barrier Breakdown
|
---|---|
Autor/in / Beteiligte Person: | Haarmann, Axel ; Deiß, Annika ; Prochaska, Jürgen ; Foerch, Christian ; Weksler, Babette ; Couraud, Pierre-olivier ; Stoll, Guido ; Rieckmann, Peter ; Buttmann, Mathias ; The Pennsylvania State University CiteSeerX Archives |
Link: | |
Zeitschrift: | ftp://ftp.ncbi.nlm.nih.gov/pub/pmc/25/6d/PLoS_One_2010_Oct_21_5(10)_e13568.tar.gz |
Medientyp: | academicJournal |
Sonstiges: |
|