Administration of a monomeric CCL2 variant to EAE mice inhibits inflammatory cell recruitment and protects from demyelination and axonal loss.
Based on gene expression data, we tested the P8A-CCL2 variant of the chemokine CCL2, able to interfere with the chemotactic properties of the parental molecule, in relapsing-remitting (RR)-EAE SJL. Only preventive treatment significantly delayed disease onset in a dose dependent manner. P8A-CCL2 administration, however, decreased demyelination, axonal loss and number of CNS infiltrating T cells and macrophages. Immunological analysis revealed that P8A-CCL2 does not act on Ag-specific T cell proliferation and does not interfere with the differentiation of IFNgamma-releasing effectors T cells. These results suggest that the therapeutic mechanism of P8A-CCL2 may rely on interference with immune cell recruitment.
Brini
E
E
Neuroimmunology Unit - INSpe, Milan, Italy.
Ruffini
F
F
Bergami
A
A
Brambilla
E
E
Dati
G
G
Greco
B
B
Cirillo
R
R
Proudfoot
A E I
AE
Comi
G
G
Furlan
R
R
Zaratin
P
P
Martino
G
G
D000328:Adult; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D018932:Chemokine CCL2 / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000276:immunology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D007371:Interferon-gamma / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009186:Myelin Sheath / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014855:Wallerian Degeneration / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D007155:Immunologic Factors; D018696:Neuroprotective Agents; D007371:Interferon-gamma