Dual role of ALCAM in neuroinflammation and blood–brain barrier homeostasis
| Autor: | Ruth Lyck, Sandra Larouche, Catherine Larochelle, Neda Haghayegh Jahromi, Elizabeth Gowing, Marc-André Lécuyer, Laure Michel, Marc Charabati, Olivia Saint-Laurent, Michael Abadier, Camille L. Pittet, Stephanie Zandee, Britta Engelhardt, Lyne Bourbonnière, Alexandre Prat |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Encephalomyelitis Autoimmune Experimental Biology Blood–brain barrier Severity of Illness Index Myelin oligodendrocyte glycoprotein 03 medical and health sciences 0302 clinical medicine Activated-Leukocyte Cell Adhesion Molecule medicine Animals Homeostasis Cells Cultured Neuroinflammation ALCAM Mice Knockout Tight Junction Proteins Multidisciplinary Tight junction Cell adhesion molecule Experimental autoimmune encephalomyelitis Endothelial Cells medicine.disease Peptide Fragments Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Spinal Cord PNAS Plus nervous system Blood-Brain Barrier Immunology cardiovascular system biology.protein Female Myelin-Oligodendrocyte Glycoprotein 030217 neurology & neurosurgery |
| Zdroj: | Proceedings of the National Academy of Sciences. 114 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|