Article abstract
Nature Immunology 9, 137 - 145 (2007)
Published online: 23 December 2007 | doi:10.1038/ni1551
Activated leukocyte cell adhesion molecule promotes leukocyte trafficking into the central nervous system
Romain Cayrol1, Karolina Wosik1, Jennifer L Berard2, Aurore Dodelet-Devillers1, Igal Ifergan1, Hania Kebir1, Arsalan S Haqqani3, Katharina Kreymborg4, Sebastian Krug1, Robert Moumdjian5, Alain Bouthillier5, Burkhard Becher4, Nathalie Arbour1, Samuel David2, Danica Stanimirovic3 & Alexandre Prat1,6
Abstract
Adhesion molecules of the immunoglobulin superfamily are crucial effectors of leukocyte trafficking into the central nervous system. Using a lipid raft-based proteomic approach, we identified ALCAM as an adhesion molecule involved in leukocyte migration across the blood-brain barrier (BBB). ALCAM expressed on BBB endothelium localized together with CD6 on leukocytes and with BBB endothelium transmigratory cups. ALCAM expression on BBB cells was upregulated in active multiple sclerosis and experimental autoimmune encephalomyelitis lesions. Moreover, ALCAM blockade restricted the transmigration of CD4+ lymphocytes and monocytes across BBB endothelium in vitro and in vivo and reduced the severity and delayed the time of onset of experimental autoimmune encephalomyelitis. Our findings indicate an important function for ALCAM in the recruitment of leukocytes into the brain and identify ALCAM as a potential target for the therapeutic dampening of neuroinflammation.
- Neuroimmunology Research Laboratory, Center for Excellence in Neuromics, Centre Hospitalier de l'Université de Montréal–Notre-Dame Hospital, Université de Montréal, H2L 4M1, Montréal, Québec, Canada.
- Center for Research in Neuroscience, McGill University Health Center, H3G 1A4, Montréal, Québec, Canada.
- Institute for Biological Sciences, National Research Council of Canada, K1A 0R6, Ottawa, Ontario, Canada.
- Neuroimmunology Division, University of Zurich, 8057 Zurich, Switzerland.
- Department of Neurosurgery, Centre Hospitalier de l'Université de Montréal–Notre-Dame Hospital, Université de Montréal, H2L 4M1, Montréal, Québec, Canada.
- Multiple Sclerosis Clinic, Department of Neurology, Centre Hospitalier de l'Université de Montréal–Notre-Dame Hospital, H2L 4M1, Montréal, Québec, Canada.
Correspondence to: Alexandre Prat1,6 e-mail: a.prat@umontreal.ca
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