Inhibition of fractalkine ameliorates murine collagen-induced arthritis.
Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with massive infiltration of inflammatory cells in the synovium of multiple joints. We and others have shown that fractalkine (FKN/CX3CL1), a chemokine expressed on fibroblast-like synoviocytes and endothelial cells in RA synovium, may contribute to the accumulation of T cells, macrophages, and dendritic cells, which express CX3CR1, the receptor for FKN. This interaction might be involved in adhesion of the inflammatory cells to endothelial cells, migration into the synovium, and cytokine production. In this study, we examined the effect of FKN inhibition on murine collagen-induced arthritis. Anti-FKN mAb significantly lowered clinical arthritis score compared with control Ab, and reduced infiltration of inflammatory cells and bone erosion in the synovium. However, anti-FKN mAb did not affect the production of either serum anti-collagen type II (CII) IgG or IFN-gamma by CII-stimulated splenic T cells. Furthermore, treatment with anti-FKN mAb inhibited migration of adoptively transferred splenic macrophages into the inflamed synovium. Our results suggest that anti-FKN mAb ameliorates arthritis by inhibiting infiltration of inflammatory cells into the synovium. Thus, FKN can be a new target molecule for the treatment of RA.
Nanki
Toshihiro
T
Department of Medicine and Rheumatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. nanki.rheu@tmd.ac.jp
Urasaki
Yasuyo
Y
Imai
Toshio
T
Nishimura
Miyuki
M
Muramoto
Kenzo
K
Kubota
Tetsuo
T
Miyasaka
Nobuyuki
N
D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D000073883:CX3C Chemokine Receptor 1; D002417:Cattle; D002464:Cell Migration Inhibition; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D024043:Collagen Type II / Q000008:administration & dosage / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000096:biosynthesis; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D051379:Mice; D008811:Mice, Inbred DBA; D019707:Receptors, Chemokine / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D024043:Collagen Type II; C515539:Cx3cl1 protein, mouse; C471885:Cx3cr1 protein, mouse; D007074:Immunoglobulin G; D008565:Membrane Proteins; D019707:Receptors, Chemokine; D007371:Interferon-gamma