2008 Brain Star Award Recipient - Cayrol Romain
Recipient
Cayrol Romain - Biosketch
Neuroimmunology PhD
Université de Montreal
Article
Cayrol R, Wosik K, Berard JL, Dodelet-Devillers A, Ifergan I, Kebir H, Haqqani AS, Kreymborg K, Krug S, Moumdjian R, Bouthillier A, Becher B, Arbour N, David S, Stanimirovic D, Prat A. Activated leukocyte cell adhesion molecule promotes leukocyte trafficking into the central nervous system. Nat Immunol. 2008 Feb;9(2):137-45. Epub 2007 Dec 23.
Significance of the paper
Adhesion molecules of the immunoglobulin super family are crucial effectors of leukocyte trafficking across vascular beds and into the central nervous system (CNS). In this paper we describe a novel cell adhesion molecule of the blood brain barrier, activated leukocyte cell adhesion molecule (ALCAM). ALCAM was previously known as an adhesion molecule expressed by many different cell types and associated with some cancers and with antigen presenting cells-lymphocyte contacts. Using a lipid raft-based proteomic approach, we identify ALCAM as a cell adhesion molecule involved in leukocyte migration across the blood-brain barrier (BBB). ALCAM is expressed on BBB endothelium, located at intercellular junctions, and co-localizes with it's ligand on leukocytes during transmigration of immune cells across an endothelial monolayer. We demonstrate, in vitro and in situ, that ALCAM expression can be up-regulated with inflammation on the neurovasculature, in active multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis (EAE, the MS animal model) lesions. Furthermore ALCAM blocking antibodies significantly reduced the transmigration of leukocytes in vitro and in vivo, and reduced the severity of EAE.
Our findings point to an important role for ALCAM in BBB permeability to leukocytes and identify ALCAM as a potential target to therapeutically dampen neuroinflammation.