Contrasting roles of plasminogen deficiency in different rheumatoid arthritis models

Abstract

Objective. To investigate the contrasting roles of plasminogen deficiency between models of collageninduced 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 plasminogendeficient 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.Conclusion. 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.

Expression Patterns of Neurotrophins and Neurotrophin Receptors in Articular Chondrocytes and Inflammatory Infiltrates in Knee Joint Arthritis

“…1 a). In the arthritic group, marked changes in morphology were observed [Li et al, 2005]. Thus, not least was the articular cartilage influenced.…”

“…The induction method for the arthritis has been described previously [Li et al, 2005]. Briefly, arthritis was induced in all 23 mice on days 0 and 7 by intradermal injection of 100 g CII emulsified in 0.1 ml complete Freund's adjuvant, containing 200 mg mycobacterium strain H37RA, at the base of the tail.…”

“…The model is very similar to the model of collagen-induced arthritis, except that in LIA, locally induced joint affection is also included. The model has been found very useful in evaluating the arthritic process in mice [Li et al, 2005].…”

Emerging roles of serine proteinases in tissue turnover in arthritis

“…In some models, deletion of uPA, plasminogen, or tPA exacerbated arthritis, with increased fibrin accumulation in the joint (31,33), while uPA or plasminogen deletion in other models resulted in only mild disease (31,34,35). The reasons for such conflicting observations are unknown, but the differences may be partly attributable to the different pathologies reported in the models used (32).…”

Protective effects of plasmin(ogen) in a mouse model of Staphylococcus aureus–induced arthritis

“…The plasminogen activator (PA) system is a general proteolytic system that has been suggested to play an important role in the development of different types of arthritis (4)(5)(6). Plasminogen can be activated to the broadspectrum protease plasmin by either of the 2 physiologic PAs, tissue-type PA (tPA) or urokinase-type PA (uPA).…”