Print Email Facebook Twitter Targeting the tetraspanin CD81 blocks monocyte transmigration and ameliorates EAE Title Targeting the tetraspanin CD81 blocks monocyte transmigration and ameliorates EAE Author Dijkstra, S. Kooij, G. Verbeek, R. van der Pol, S.M.A. Amor, S. Geisert Jr., E.E. Dijkstra, C.D. van Noort, J.M. Vries, H.E.D. TNO Kwaliteit van Leven Publication year 2008 Abstract Leukocyte infiltration is a key step in the development of demyelinating lesions in multiple sclerosis (MS), and molecules mediating leukocyte-endothelial interactions represent prime candidates for the development of therapeutic strategies. Here we studied the effects of blocking the integrin-associated tetraspanin CD81 in in vitro and in vivo models for MS. In an in vitro setting mAb against CD81 significantly reduced monocyte transmigration across brain endothelial cell monolayers, both in rodent and human models. Interestingly, leukocyte as well as endothelial CD81 was involved in this inhibitory effect. To assess their therapeutic potential, CD81 mAb were administered to mice suffering from experimental autoimmune encephalomyelitis (EAE). We found that Eat2, but not 2F7 mAb directed against mouse CD81 significantly reduced the development of neurological symptoms of EAE when using a preventive approach. Concomitantly, Eat2 treated animals showed reduced inflammation in the spinal cord. We conclude that CD81 represents a potential therapeutic target to interfere with leukocyte infiltration and ameliorate inflammatory neurological damage in MS. © 2008 Elsevier Inc. All rights reserved. Subject BiologyBiomedical ResearchCD81EAEMultiple sclerosisTetraspaninsTherapeutic antibodiesTransendothelial migrationCD81 antigenmonoclonal antibodymonoclonal antibody 1 3 3 22monoclonal antibody 1D6monoclonal antibody 2F7monoclonal antibody AMP1monoclonal antibody CD81monoclonal antibody Eat2monoclonal antibody JS81monoclonal antibody TA2tetraspaninunclassified drugvery late activation antigen 4 antibodyallergic encephalomyelitisanimal cellanimal experimentanimal modelanimal tissueantiinflammatory activityarticlecontrolled studydrug effectendothelium cellfemalehumanhuman cellin vitro studyin vivo studymonocytemonolayer culturemousemyelitisneurologic diseaseneutrophil chemotaxisnonhumanpriority journalprotein targetingrattreatment outcomeAnimalsAntibodies, MonoclonalAntigens, CDBlood-Brain BarrierCell Line, TransformedCerebral ArteriesChemotaxis, LeukocyteDisease Models, AnimalEncephalomyelitis, Autoimmune, ExperimentalEndothelial CellsFemaleHumansImmunosuppressionImmunosuppressive AgentsMiceMonocytesMultiple SclerosisRatsTreatment Outcome To reference this document use: http://resolver.tudelft.nl/uuid:a60a7b85-a1a5-4319-aa87-a406f482360c DOI https://doi.org/10.1016/j.nbd.2008.05.018 TNO identifier 240992 ISSN 0969-9961 Source Neurobiology of Disease, 31 (3), 413-421 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.