Modulation of experimental autoimmune encephalomyelitis by VLA-2 blockade.
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Adhesion molecules play important roles in cell-cell and cell-extracellular matrix (ECM) interactions in inflammation. Blocking the interaction between inflammatory cells and vascular endothelia can prevent cell entry into tissues and harmful inflammatory responses, that is, autoimmunity, but could also limit immunosurveillance by anti-viral T cells in sites of infection or latency. Development of progressive multifocal leukoencephalopathy in patients treated with antibody against very late antigen (VLA)-4 prompted us to explore an alternative therapeutic approach. We used an antibody against the integrin alpha2, VLA-2, that interacts with ECM, not vascular endothelium. SJL/J mice were sensitized with myelin proteolipid protein (PLP)(139-151) peptide to induce experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Treatment of mice with VLA-2 antibody suppressed clinical signs and CNS inflammation of EAE, when antibody was given immediately after disease onset. In contrast, VLA-4 or VLA-2 antibody treatment of mice during the priming or remission phase of EAE had minor effects on the disease's clinical course. No differences were found in lymphoproliferative responses to PLP(139-151) among treatment groups. Data suggest that blocking cell-ECM interactions can be an alternative therapy for MS.
Tsunoda
Ikuo
I
Department of Neurology, University of Utah School of Medicine, Salt Lake City, Utah 84132-2305, USA.
Terry
Emily Jane
EJ
Marble
Benjamin J
BJ
Lazarides
Elias
E
Woods
Catherine
C
Fujinami
Robert S
RS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology*; D002490:Central Nervous System / Q000276:immunology*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D038982:Integrin alpha2beta1 / Q000037:antagonists & inhibitors / Q000276:immunology*; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors / Q000276:immunology; D051379:Mice; D009103:Multiple Sclerosis / Q000276:immunology*
D000911:Antibodies, Monoclonal; D038982:Integrin alpha2beta1; D039041:Integrin alpha4beta1