title: Contrasting roles of plasminogen deficiency in different rheumatoid arthritis models.
abstract: OBJECTIVE
  To investigate the contrasting roles of plasminogen deficiency between models of collagen-induced arthritis (CIA) and antigen-induced arthritis (AIA).
  
  
  METHODS
  We developed a new animal model of arthritis, which we have called local injection-induced arthritis (LIA). In this model, we replaced methylated bovine serum albumin, which is normally used as an immunogen and is injected intraarticularly into the knee joint, with type II collagen (CII) to induce AIA. The severity of CIA, LIA, and AIA in wild-type and plasminogen-deficient mice was evaluated by clinical scoring or histologic grading. Necrosis was determined by histology and immunohistochemistry.
  
  
  RESULTS
  After CII immunization alone, wild-type mice developed arthritis in most of the paws as well as in the knee joints, whereas plasminogen-deficient mice were totally resistant to the disease. Local knee injections of CII or saline slightly enhanced the severity of the knee arthritis in wild-type mice during a 60-day experimental period. Unexpectedly, the plasminogen-deficient mice also developed arthritis in joints that were injected with CII or saline. However, the arthritis was milder than that in their wild-type littermates. Sustained tissue necrosis was found only in the plasminogen-deficient mice after the local injection.
  
  
  CONCLUSIONS
  Our data show that both the antigen and the joint trauma caused by the local injection are critical to explaining the contrasting roles of plasminogen deficiency in CIA and AIA. This further indicates that CIA and AIA have distinct pathogenic mechanisms. The data also suggest that plasmin may be required for the induction of these arthritis models that are critically dependent on complement activation.
authors.affiliation: Umeå University, Sweden.
authors.forename: Jinan
authors.initials: J
authors.lastname: Li
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Guo
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
authors.forename: Tor
authors.initials: T
authors.lastname: Ny
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism* / Q000503:physiopathology; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D024043:Collagen Type II / Q000008:administration & dosage / Q000276:immunology; D004195:Disease Models, Animal; D007114:Immunization; D007270:Injections, Intra-Articular; D007718:Knee Injuries / Q000150:complications; D007719:Knee Joint; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009336:Necrosis; D010958:Plasminogen / Q000172:deficiency*; D012720:Severity of Illness Index; D012965:Sodium Chloride / Q000008:administration & dosage; D013583:Synovial Membrane / Q000473:pathology
chemical_list: D024043:Collagen Type II; D012965:Sodium Chloride; D010958:Plasminogen