RESEARCH - Contrasting roles of plasminogen deficiency in different RA models

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Arthritis Rheum. 2005 Aug;52(8):2541-8.

Contrasting roles of plasminogen deficiency in different rheumatoid

arthritis models.

Li J, Guo Y, Holmdahl R, Ny T.

Umea University, Umea, Sweden.

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.

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.

PMID: 16052596

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

6052596 & dopt=Abstract

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