title: Circulating C3 is necessary and sufficient for induction of autoantibody-mediated arthritis in a mouse model.
abstract: OBJECTIVE
  For the inflammation characteristic of rheumatoid arthritis, the relative contribution of mediators produced locally in the synovium versus those circulating systemically is unknown. Complement factor C3 is made in rheumatoid synovium and has been proposed to be a crucial driver of inflammation. The aim of this study was to test, in a mouse model of rheumatoid arthritis, whether C3 synthesized within the synovium is important in promoting inflammation.
  
  
  METHODS
  Radiation bone marrow chimeras between normal and C3(-/-) mice were constructed in order to generate animals that expressed or lacked expression of C3 only in hematopoietic cells. Parabiotic mice were made by surgically linking C3(-/-) mice to irradiated wild-type mice to obtain animals having C3 only in the circulation. Arthritis was induced by injection of serum from arthritic K/BxN mice.
  
  
  RESULTS
  In bone marrow chimeras, synthesis of C3 by radioresistant cells was necessary and sufficient to confer susceptibility to serum-transferred arthritis. Parabionts having C3 only in the circulation remained sensitive to arthritis induction, and the cartilage of these arthritic mice contained deposits of C3.
  
  
  CONCLUSIONS
  In a mouse model in which the alternative pathway of complement activation is critical to the induction of arthritis by autoantibodies, circulating C3 was necessary and sufficient for arthritis induction.
authors.affiliation: Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Monach
authors.forename: Admar
authors.initials: A
authors.lastname: Verschoor
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Jacobs
authors.forename: Michael C
authors.initials: MC
authors.lastname: Carroll
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Wagers
authors.forename: Christophe
authors.initials: C
authors.lastname: Benoist
authors.forename: Diane
authors.initials: D
authors.lastname: Mathis
mesh_terms: D000818:Animals; D001168:Arthritis / Q000097:blood* / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D003176:Complement C3 / Q000032:analysis*; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D001323:Autoantibodies; D003176:Complement C3