Dual role of ALCAM in neuroinflammation and blood–brain barrier homeostasis
| العنوان: | Dual role of ALCAM in neuroinflammation and blood–brain barrier homeostasis |
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| المؤلفون: | 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 |
| المصدر: | Proceedings of the National Academy of Sciences. 114 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| تدمد: | 1091-6490 0027-8424 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::481c93b41cf8f2c1137425dedebc6b37Test https://doi.org/10.1073/pnas.1614336114Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....481c93b41cf8f2c1137425dedebc6b37 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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