Details

Autor(en) / Beteiligte

• Lécuyer, Marc-André
• Saint-Laurent, Olivia
• Bourbonnière, Lyne
• Larouche, Sandra
• Larochelle, Catherine
• Michel, Laure
• Charabati, Marc
• Abadier, Michael
• Zandee, Stephanie
• Jahromi, Neda Haghayegh
• Gowing, Elizabeth
• Pittet, Camille
• Lyck, Ruth
• Engelhardt, Britta
• Prat, Alexandre

Titel

Dual role of ALCAM in neuroinflammation and blood—brain barrier homeostasis

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2017-01, Vol.114 (4), p.E524-E533

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2017

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Activated leukocyte cell adhesion molecule (ALCAM) is a cell adhesion molecule found on blood–brain barrier endothelial cells (BBB-ECs) that was previously shown to be involved in leukocyte transmigration across the endothelium. In the present study, we found that ALCAM knockout (KO) mice developed a more severe myelin oligodendrocyte glycoprotein (MOG)35–55–induced experimental autoimmune encephalomyelitis (EAE). The exacerbated disease was associated with a significant increase in the number of CNS-infiltrating proinflammatory leukocytes compared with WT controls. Passive EAE transfer experiments suggested that the pathophysiology observed in active EAE was linked to the absence of ALCAM on BBB-ECs. In addition, phenotypic characterization of unimmunized ALCAM KO mice revealed a reduced expression of BBB junctional proteins. Further in vivo, in vitro, and molecular analysis confirmed that ALCAM is associated with tight junction molecule assembly at the BBB, explaining the increased permeability of CNS blood vessels in ALCAM KO animals. Collectively, our data point to a biologically important function of ALCAM in maintaining BBB integrity.