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

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.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::481c93b41cf8f2c1137425dedebc6b37Test
https://doi.org/10.1073/pnas.1614336114Test

المؤلفون: Alexandres Prat, Michael Abadier, Marc-André Lécuyer, Urban Deutsch, Ana Bélen Garcia Martin, Christof B. Wyss, Britta Engelhardt, Gaby Enzmann, Fabien Gosselet, Ruth Lyck, Nicole Schaeren-Wiemers, Joshua A. Weiner, Maria Rosito, Federica Sallusto, Christoph Matti, Thomas Zeis, Laure Michel

المساهمون: Theodor Kocher Institute, University of Bern, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), University Hospital Basel [Basel], Institute for Research in Biomedicine, Laboratoire de la Barrière Hémato-Encéphalique (LBHE), Université d'Artois (UA), University of Iowa [Iowa City]

المصدر: Journal of Cerebral Blood Flow and Metabolism
Journal of Cerebral Blood Flow and Metabolism, Nature Publishing Group, 2017, 37 (8), pp.2894-2909. ⟨10.1177/0271678X16678639⟩

مصطلحات موضوعية: 0301 basic medicine, Pathology, Leukocyte migration, alcam, blood–brain barrier, immune cell extravasation, multiple sclerosis, neuroinflammation, animals, antigens, cd, blood-brain barrier, cell adhesion molecules, neuronal, cells, cultured, encephalomyelitis, autoimmune, experimental, endothelial cells, endothelium, vascular, fetal proteins, humans, mice, inbred c57bl, knockout, monocytes, t-lymphocytes, transendothelial and transepithelial migration, [SDV]Life Sciences [q-bio], 0302 clinical medicine, 610 Medicine & health, T cell extravasation, Cells, Cultured, Mice, Knockout, Experimental autoimmune encephalomyelitis, Activated-Leukocyte Cell Adhesion Molecule, Extravasation, Cell biology, medicine.anatomical_structure, Neurology, cardiovascular system, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Encephalomyelitis, Autoimmune, Experimental, Cell Adhesion Molecules, Neuronal, Biology, Blood–brain barrier, 03 medical and health sciences, Antigens, CD, medicine, ALCAM, Neuroinflammation, Original Articles, medicine.disease, Mice, Inbred C57BL, 030104 developmental biology, Neurology (clinical), Endothelium, Vascular, 030217 neurology & neurosurgery

الوصف: Activated leukocyte cell adhesion molecule (ALCAM) has been proposed to mediate leukocyte migration across the blood–brain barrier (BBB) in multiple sclerosis or experimental autoimmune encephalomyelitis (EAE). Here, we confirmed vascular ALCAM expression in human brain tissue samples in situ and on two different human in vitro BBB models. Antibody-mediated inhibition of ALCAM reduced diapedesis of human CD4+ Th1 but not of Th17 cells across the human BBB in vitro. In accordance to human Th1 cells, mouse Th1 cells showed reduced diapedesis across an ALCAM−/− in vitro BBB model under static but no longer under flow conditions. In contrast to the limited role of ALCAM in T cell extravasation across the BBB, we found a contribution of ALCAM to rolling, adhesion, and diapedesis of human CD14+ monocytes across the human BBB under flow and static conditions. Taken together, our study highlights the potential differences in the CNS expression of ALCAM in mouse and human and supports a prominent role for ALCAM in the multi-step extravasation of monocytes across the BBB.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3fbcebcff048c33494fce282ab9d3b8dTest
http://hdl.handle.net/11573/1608970Test