title: Membrane complement regulators protect against the development of type II collagen-induced arthritis in rats.
abstract: OBJECTIVE
  To investigate changes in the distribution patterns of membrane complement regulators (MCRs) during the development of type II collagen-induced arthritis (CIA) and to examine the protective effects of these molecules against the augmentation of CIA in the knee joint.
  
  
  METHODS
  Immunohistochemistry was used to examine the distribution of the MCRs Crry, DAF, and CD59 in the synovium of knee joints before and 2, 4, and 10 weeks after induction of CIA by immunization with type II collagen. In addition, at 2 or 10 weeks after induction of CIA, rats were injected intraarticularly with anti-Crry and/or anti-CD59 as the F(ab')2 fraction of monoclonal antibodies (mAb). Knee joint swelling and histologic changes in the synovium were examined 2 weeks after mAb injection.
  
  
  RESULTS
  Synovial expression of Crry, DAF, and CD59 decreased in parallel with increased inflammation. When Crry and CD59 were functionally blocked at 2 weeks after the induction of CIA, swelling of the knee joints was markedly increased. Blocking of either regulator alone had no effect on swelling. Thickening of the synovial surface and proliferation of subsynovial tissue were all increased after blocking Crry and CD59, whereas blocking of either MCR alone had no effect. When both Crry and CD59 were blocked, deposits of membrane attack complex were found in the synovium.
  
  
  CONCLUSIONS
  Our findings indicate that in rats with CIA and severely inflamed synovium, local expression of MCR is reduced. The MCRs Crry and CD59 appear to suppress the development of CIA.
authors.affiliation: The Third Department of Internal Medicine, Nagoya University School of Medicine, Japan. mmizu@med.nagoya-u.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Mizuno
authors.forename: K
authors.initials: K
authors.lastname: Nishikawa
authors.forename: O B
authors.initials: OB
authors.lastname: Spiller
authors.forename: B P
authors.initials: BP
authors.lastname: Morgan
authors.forename: N
authors.initials: N
authors.lastname: Okada
authors.forename: H
authors.initials: H
authors.lastname: Okada
authors.forename: S
authors.initials: S
authors.lastname: Matsuo
mesh_terms: D000818:Animals; D001168:Arthritis / Q000209:etiology / Q000276:immunology*; D024043:Collagen Type II / Q000276:immunology*; D007150:Immunohistochemistry; D051381:Rats; D011951:Receptors, Complement / Q000276:immunology*
chemical_list: D024043:Collagen Type II; D011951:Receptors, Complement