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Targeting the tetraspanin CD81 blocks monocyte transmigration and ameliorates EAE

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Author: Dijkstra, S. · Kooij, G. · Verbeek, R. · Pol, S.M.A. van der · Amor, S. · Geisert Jr., E.E. · Dijkstra, C.D. · Noort, J.M. van · Vries, H.E.d.
Institution: TNO Kwaliteit van Leven
Source:Neurobiology of Disease, 3, 31, 413-421
Identifier: 240992
doi: doi:10.1016/j.nbd.2008.05.018
Keywords: Biology · Biomedical Research · CD81 · EAE · Multiple sclerosis · Tetraspanins · Therapeutic antibodies · Transendothelial migration · CD81 antigen · monoclonal antibody · monoclonal antibody 1 3 3 22 · monoclonal antibody 1D6 · monoclonal antibody 2F7 · monoclonal antibody AMP1 · monoclonal antibody CD81 · monoclonal antibody Eat2 · monoclonal antibody JS81 · monoclonal antibody TA2 · tetraspanin · unclassified drug · very late activation antigen 4 antibody · allergic encephalomyelitis · animal cell · animal experiment · animal model · animal tissue · antiinflammatory activity · article · controlled study · drug effect · endothelium cell · female · human · human cell · in vitro study · in vivo study · monocyte · monolayer culture · mouse · myelitis · neurologic disease · neutrophil chemotaxis · nonhuman · priority journal · protein targeting · rat · treatment outcome · Animals · Antibodies, Monoclonal · Antigens, CD · Blood-Brain Barrier · Cell Line, Transformed · Cerebral Arteries · Chemotaxis, Leukocyte · Disease Models, Animal · Encephalomyelitis, Autoimmune, Experimental · Endothelial Cells · Female · Humans · Immunosuppression · Immunosuppressive Agents · Mice · Monocytes · Multiple Sclerosis · Rats · Treatment Outcome


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.