The plasminogen activator/plasmin system is essential for development of the joint inflammatory phase of collagen type II-induced arthritis

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The plasminogen activator (PA) system has been proposed to have important roles in rheumatoid arthritis. Here we have used the autoinumme collagen type II (CII)-induced arthritis (CIA) model and mice deficient for urokinase-type PA (uPA) or plasminogen to investigate the role of the PA system for development of arthritis. Our data revealed that uPA-deficient mice have a lower severity and incidence of CIA than wildtype mice. Furthermore, although >80% of wild-type control mice developed CIA, we found that none of the 50 plasminogen-deficient littermates that were tested developed CIA within a 40-day period. Antibody generation after CH immunization as well as the binding of labeled anti-CII antibodies to the surface of cartilage were similar in wild-type and plasminogen-deficient mice. No sign of inflammation was seen when plasminogen-deficient mice were injected with a mixture of monoclonal antibodies against CH. However, after daily injections of human plasminogen, these mice developed arthritis within 5 days. Our finding that infiltration of inflammatory cells into the synovial joints was impaired in plasminogen-deficient mice suggests that uPA and plasminogen are important mediators of joint inflammation. Active plasmin is therefore essential for the induction of pathological inflammatory joint destruction in CIA.


  • JN Li
  • A Ny
  • G Leonardsson
  • KS Nandakumar
  • Rikard Holmdahl
  • T Ny
Enheter & grupper

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cell- och molekylärbiologi
Sidor (från-till)783-792
TidskriftAmerican Journal of Pathology
StatusPublished - 2005
Peer review utfördJa