title: Essential role of Fc gamma receptors in anti-type II collagen antibody-induced arthritis.
abstract: Anti-type II collagen (anti-CII) Ab is a well-known autoantibody observed in patients with rheumatoid arthritis. Injection of anti-CII Ab and LPS induces arthritis in mice in which anti-CII Ab as well as inflammatory cytokines, IL-1beta and TNF-alpha, play critical roles. We investigated the involvement of IgG FcRs (FcgammaRs) in this arthritis model. BALB/c mice injected with the F(ab')(2) of anti-CII Ab showed no signs of arthritis. Arthritis development was not observed in FcRgamma(-/-) mice and was partially suppressed in FcgammaRIII(-/-) mice despite the binding of anti-CII Ab and C3 to cartilage surface. Surprisingly, BALB/c mice lacking FcgammaRIIB, which is known as an inhibitory FcgammaR, developed arthritis with no exacerbation in arthritis score compared with wild-type (WT) mice, and only slight exacerbation was observed in the histopathological analysis. In contrast, aged FcgammaRIIB(-/-) BALB/c mice developed arthritis without LPS injection, suggesting an augmented susceptibility to arthritis in aged FcgammaRIIB(-/-) mice. No significant difference was observed among BALB/c-WT, -FcRgamma(-/-), and -FcgammaRIIB(-/-) mice on cytokine production induced by anti-CII Ab and LPS injection. Severe arthritis developed in BALB/c-WT and -FcgammaRIIB(-/-) mice, but not in BALB/c-FcRgamma(-/-) mice, after the injection of anti-CII Ab and inflammatory cytokines. These results suggest that the reason behind the nondevelopment of arthritis in FcRgamma(-/-) BALB/c mice is not due to a disorder in transient cytokine production, but to an irregularity downstream of cytokine production.
authors.affiliation: Biological Research Laboratories, Sankyo Co., Ltd., Shinagawa-ku, Tokyo, Japan. tkagar@shina.sankyo.co.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Kagari
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tanaka
authors.forename: Hiromi
authors.initials: H
authors.lastname: Doi
authors.forename: Takaichi
authors.initials: T
authors.lastname: Shimozato
mesh_terms: D000375:Aging / Q000235:genetics / Q000276:immunology; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D001323:Autoantibodies / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D001666:Binding Sites, Antibody / Q000235:genetics / Q000276:immunology; D002358:Cartilage, Articular / Q000276:immunology / Q000378:metabolism; D024043:Collagen Type II / Q000276:immunology*; D003176:Complement C3 / Q000378:metabolism; D004338:Drug Combinations; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage; D007275:Injections, Intravenous; D007375:Interleukin-1 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D015703:Antigens, CD; D001323:Autoantibodies; D024043:Collagen Type II; D003176:Complement C3; D004338:Drug Combinations; C080571:Fc gamma receptor IIB; D007140:Immunoglobulin Fab Fragments; D007375:Interleukin-1; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha