title: Essential role of neutrophils in anti-type II collagen antibody and lipopolysaccharide-induced arthritis.
abstract: In mice arthritis model induced by anti-type II collagen (CII) antibodies and lipopolysaccharide (LPS), most of cells that infiltrated into the joint space were neutrophils. To investigate the role of neutrophils in the pathogenesis of arthritis, we depleted the neutrophils in vivo by injection of the antibody against Gr-1 expressed mainly on neutrophils. The neutrophil depletion completely inhibited the arthritis development. Furthermore, neutrophil depletion in mice that had already developed arthritis ameliorated the disease. These results showed that neutrophils are indispensable not only for the development, but also for the maintenance of arthritis. Next, we tried to develop arthritis in C5-deficient mice to investigate the involvement of C5a, one of chemotactic factors for neutrophils. C5-deficient mice showed significant reduction in arthritis development in comparison with wild type mice. Injection of pertussis toxin (Ptx) into the mice, which inhibits the signals from the inhibitory G-protein coupled-receptors including the C5a receptor, suppressed the development of arthritis. Furthermore, Ptx also ameliorated the arthritis when injected into mice that had already developed the disease. These results suggest the important role of chemotactic factors involving C5a and inhibitory G-protein (Gi)-coupled receptors not only in the development, but also in the maintenance of arthritis.
authors.affiliation: Biological Research Laboratories, Sankyo Co., Ltd, Tokyo, Japan. dtanaka@sankyo.co.jp
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tanaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Kagari
authors.forename: Hiromi
authors.initials: H
authors.lastname: Doi
authors.forename: Takaichi
authors.initials: T
authors.lastname: Shimozato
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001169:Arthritis, Experimental / Q000209:etiology / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D024043:Collagen Type II / Q000276:immunology; D003182:Complement C5 / Q000172:deficiency / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D037342:Pertussis Toxin / Q000494:pharmacology / Q000627:therapeutic use; D019707:Receptors, Chemokine / Q000276:immunology; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013583:Synovial Membrane / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D024043:Collagen Type II; D003182:Complement C5; C503133:Gr-1 protein, mouse; D008070:Lipopolysaccharides; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; D037342:Pertussis Toxin