An essential role for CCL3 in the development of collagen antibody-induced arthritis.
CCL3 is a C-C family chemokine detected at high levels in the synovial tissue and fluids of rheumatoid arthritis (RA) patients. CCL3 binds to the chemokine receptors CCR1 and CCR5, which are expressed by inflammatory leukocytes such as macrophages and T cells present in the affected joints of RA patients. The present study was undertaken to investigate whether absence of CCL3 prevented development of inflammation and joint destruction in anti-type II collagen monoclonal antibody (anti-CII mAb)-induced arthritis. "CCL3 null mice were different from wild-type control mice in terms of body weight loss". In addition, CCL3 null mice exhibited milder clinical and histopathological scores following administration of anti-CII mAb and endotoxin. Moreover, the release of TNF in response to systemic administration of endotoxin was not affected in CCL3 null mice compared to wild-type mice, indicating that the phenotype was not attributable to a defect in endotoxin response. These results indicate that CCL3 plays an essential role in the development of inflammation and joint destruction induced by anti-CII mAb.
Chintalacharuvu
Subba Rao
SR
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA. chinne@lilly.com
Wang
Jian X
JX
Giaconia
Joseph M
JM
Venkataraman
Chandrasekar
C
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology*; D001835:Body Weight; D002356:Cartilage / Q000276:immunology / Q000473:pathology; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC / Q000235:genetics* / Q000276:immunology; D024043:Collagen Type II / Q000276:immunology; D004195:Disease Models, Animal; D004731:Endotoxins; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007596:Joints / Q000276:immunology / Q000473:pathology; D019402:Macrophage Inflammatory Proteins / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000683:Serum Amyloid P-Component / Q000032:analysis
D000911:Antibodies, Monoclonal; C496534:Ccl3 protein, mouse; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC; D024043:Collagen Type II; D004731:Endotoxins; D019402:Macrophage Inflammatory Proteins; D000683:Serum Amyloid P-Component