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

<h4>Background</h4>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 st...

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Autores principales:	Axel Haarmann, Annika Deiss, Jürgen Prochaska, Christian Foerch, Babette Weksler, Ignacio Romero, Pierre-Olivier Couraud, Guido Stoll, Peter Rieckmann, Mathias Buttmann
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/233dee5c91ae41939cac6ee1faf4d0c9
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spelling	oai:doaj.org-article:233dee5c91ae41939cac6ee1faf4d0c92021-11-18T07:03:00ZEvaluation of soluble junctional adhesion molecule-A as a biomarker of human brain endothelial barrier breakdown.1932-620310.1371/journal.pone.0013568https://doaj.org/article/233dee5c91ae41939cac6ee1faf4d0c92010-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21060661/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusion</h4>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.Axel HaarmannAnnika DeissJürgen ProchaskaChristian FoerchBabette WekslerIgnacio RomeroPierre-Olivier CouraudGuido StollPeter RieckmannMathias ButtmannPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 10, p e13568 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Axel Haarmann Annika Deiss Jürgen Prochaska Christian Foerch Babette Weksler Ignacio Romero Pierre-Olivier Couraud Guido Stoll Peter Rieckmann Mathias Buttmann Evaluation of soluble junctional adhesion molecule-A as a biomarker of human brain endothelial barrier breakdown.
description	<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusion</h4>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.
format	article
author	Axel Haarmann Annika Deiss Jürgen Prochaska Christian Foerch Babette Weksler Ignacio Romero Pierre-Olivier Couraud Guido Stoll Peter Rieckmann Mathias Buttmann
author_facet	Axel Haarmann Annika Deiss Jürgen Prochaska Christian Foerch Babette Weksler Ignacio Romero Pierre-Olivier Couraud Guido Stoll Peter Rieckmann Mathias Buttmann
author_sort	Axel Haarmann
title	Evaluation of soluble junctional adhesion molecule-A as a biomarker of human brain endothelial barrier breakdown.
title_short	Evaluation of soluble junctional adhesion molecule-A as a biomarker of human brain endothelial barrier breakdown.
title_full	Evaluation of soluble junctional adhesion molecule-A as a biomarker of human brain endothelial barrier breakdown.
title_fullStr	Evaluation of soluble junctional adhesion molecule-A as a biomarker of human brain endothelial barrier breakdown.
title_full_unstemmed	Evaluation of soluble junctional adhesion molecule-A as a biomarker of human brain endothelial barrier breakdown.
title_sort	evaluation of soluble junctional adhesion molecule-a as a biomarker of human brain endothelial barrier breakdown.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/233dee5c91ae41939cac6ee1faf4d0c9
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Evaluation of soluble junctional adhesion molecule-A as a biomarker of human brain endothelial barrier breakdown.

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