Targeting the tetraspanin CD81 blocks monocyte transmigration and ameliorates EAE.
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.
Dijkstra
S
S
Department of Molecular Cell Biology and Immunology, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. s.dijkstra@vumc.nl
Kooij
G
G
Verbeek
R
R
van der Pol
S M A
SM
Amor
S
S
Geisert
E E
EE
Dijkstra
C D
CD
van Noort
J M
JM
Vries
H E de
HE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D015703:Antigens, CD / Q000187:drug effects* / Q000276:immunology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000276:immunology; D002461:Cell Line, Transformed; D002536:Cerebral Arteries / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000276:immunology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D051381:Rats; D060225:Tetraspanin 28; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C554798:CD81 protein, human; C554799:Cd81 protein, mouse; C533665:Eat2 monoclonal antibody; D007166:Immunosuppressive Agents; D060225:Tetraspanin 28