Suppression of experimental autoimmune encephalomyelitis with a TNF binding protein (TNFbp) correlates with down-regulation of VCAM-1/VLA-4.
The effect of a novel TNF binding protein (TNFbp), a polyethylene glycol-linked form of the type I soluble receptor of TNF, on the expression of adhesion molecules has been investigated with a passive transfer model of experimental autoimmune encephalomyelitis (EAE) in SJL/J mice. The expression of L-selectin, VLA-4 and LFA-1 on spleen cells of EAE animals treated with TNFbp or saline was examined by FACS analysis. The expression of VCAM-1 and ICAM-1 was investigated by immunochemistry in spinal cord tissue of SJL/J mice with EAE. In animals sensitized for EAE and treated with TNFbp, the expression of VCAM-1 in the central nervous system as well as VLA-4 on spleen cells was clearly diminished. Reduction in VCAM-1 staining and VLA-4 expression corresponded to inhibition of inflammation in the spinal cord and to prevention of clinical signs of EAE. The results have also shown that myelin basic protein responses as well as non-antigen-specific responses were not diminished in animals treated with TNFbp. The findings suggest that TNFbp might prevent EAE development by modulating the expression of VCAM-1 and VLA-4.
Selmaj
K
K
Department of Neurology, Medical Academy of Lodz, Poland. kselmaj@afazja.am.lodz.pl
Walczak
A
A
Mycko
M
M
Berkowicz
T
T
Kohno
T
T
Raine
C S
CS
D000818:Animals; D016516:CD4-CD8 Ratio; D002352:Carrier Proteins / Q000494:pharmacology*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D016130:Immunophenotyping; D039041:Integrin alpha4beta1; D016023:Integrins / Q000096:biosynthesis*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D019041:L-Selectin / Q000096:biosynthesis; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis; D051379:Mice; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis*; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
D002352:Carrier Proteins; D039041:Integrin alpha4beta1; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D016201:Receptors, Lymphocyte Homing; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin; C069521:recombinant human tumor necrosis factor-binding protein-1