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Rheumatology 2002; 41: 136-141
© 2002 British Society for Rheumatology

Original papers

Plasminogen activator inhibitor type-1 deficiency attenuates murine antigen-induced arthritis

K. Van Ness, V. Chobaz-Péclat, M. Castellucci1, A. So and N. Busso

Centre Hospitalier Universitaire Vaudois, Laboratoire de Rhumatologie, Nestlé 05-5029, 1011 Lausanne, Switzerland and
1 Istituto di Morfologia, Universita di Ancona, Italy

Objective. To examine the role of plasminogen activator inhibitor type-1 (PAI-1), the major fibrinolytic inhibitor, in vivo during murine antigen-induced arthritis (AIA).

Methods. AIA was induced in PAI-1-deficient mice and control wild-type mice. Arthritis severity was evaluated by technetium 99m (99mTc) uptake in the knee joints and by histological scoring. Intra-articular fibrin deposition was examined by immunohistochemistry and synovial fibrinolysis quantitated by tissue D-dimer measurements and zymograms.

Results. Joint inflammation, quantitated by 99mTc uptake, was significantly reduced in PAI-1-/- mice on day 7 after arthritis onset (P<0.01). Likewise, synovial inflammation, evaluated by histological scoring, was significantly decreased in PAI-1-deficient mice on day 10 after arthritis onset (P<0.001). Articular cartilage damage was significantly decreased in PAI-1-/- mice, as shown by histological grading of safranin-O staining on day 10 after arthritis onset (P<0.005). Significantly decreased synovial accumulation of fibrin was observed by day 10 in arthritic joints of PAI-1-/- mice (P<0.005). Accordingly, the synovial tissue content of D-dimers, the specific fibrin degradation products generated by plasmin, were increased in PAI-1-/- mice (P<0.02). Finally, as expected, PA activity was increased in synovial tissues from PAI-1-/- mice, as shown by zymographic analysis.

Conclusions. These results indicate that deficiency of PAI-1 results in increased synovial fibrinolysis, leading to reduced fibrin accumulation in arthritic joints and reduced severity of AIA.

KEY WORDS: PAI-1, Rheumatoid arthritis, Mice, Fibrin, Fibrinolysis, Inflammation.

Correspondence to: N. Busso.


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