title: Essential role of neutrophils in the initiation and progression of a murine model of rheumatoid arthritis.
abstract: Neutrophils are prominent participants in the joint inflammation of human rheumatoid arthritis (RA) patients, but the extent of their role in the inductive phase of joint inflammation is unknown. In the K/BxN mouse RA model, transfer of autoreactive Ig from the K/BxN mouse into mice induces a rapid and profound joint-specific inflammatory response reminiscent of human RA. We observed that after K/BxN serum transfer, the earliest clinical signs of inflammation in the ankle joint correlated with the presence of neutrophils in the synovial regions of recipient mouse ankle joints. In this study, we investigated the role of neutrophils in the early inflammatory response to transferred arthritogenic serum from the K/BxN transgenic mouse. Mice were treated with a neutrophil-depleting mAb before and following transfer of arthritogenic serum and scored for clinical indications of inflammation and severity of swelling in ankle joints and front paws. In the absence of neutrophils, mice were completely resistant to the inflammatory effects of K/BxN serum. Importantly, depletion of neutrophils in diseased recipient mice up to 5 days after serum transfer reversed the inflammatory reaction in the joints. Transfer of serum into mice deficient in the generation of nitrogen or oxygen radicals (inducible NO synthase 2 or gp91(phox) genes, respectively) gave normal inflammatory responses, indicating that neither pathway is essential for disease induction. These studies have identified a critical role for neutrophils in initiating and maintaining inflammatory processes in the joint.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: B T
authors.initials: BT
authors.lastname: Wipke
authors.forename: P M
authors.initials: PM
authors.lastname: Allen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D002358:Cartilage, Articular / Q000473:pathology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D004487:Edema / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D006614:Hindlimb; D007106:Immune Sera / Q000008:administration & dosage / Q000235:genetics; D007116:Immunization, Passive; D007274:Injections, Intraperitoneal; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D009503:Neutropenia / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology*; D009569:Nitric Oxide / Q000172:deficiency / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D013583:Synovial Membrane / Q000473:pathology; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D007106:Immune Sera; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse