Abstract |
The plasminogen activator (PA) system has been proposed to have important roles in rheumatoid arthritis. Here we have used the autoimmune 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 wild-type 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 CII 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 CII. 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.
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Authors | Jinan Li, Annelii Ny, Göran Leonardsson, Kutty Selva Nandakumar, Rikard Holmdahl, Tor Ny |
Journal | The American journal of pathology
(Am J Pathol)
Vol. 166
Issue 3
Pg. 783-92
(Mar 2005)
ISSN: 0002-9440 [Print] United States |
PMID | 15743790
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal
- Collagen Type II
- Epitopes
- Plasminogen
- Plasminogen Activators
- Fibrinolysin
- Urokinase-Type Plasminogen Activator
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Topics |
- Animals
- Antibodies, Monoclonal
(chemistry)
- Arthritis
(immunology, pathology)
- Arthritis, Experimental
(immunology, pathology)
- Collagen Type II
(metabolism)
- Enzyme-Linked Immunosorbent Assay
- Epitopes
- Fibrinolysin
(metabolism)
- Immunohistochemistry
- Inflammation
(metabolism)
- Joints
(immunology)
- Mice
- Mice, Inbred C57BL
- Plasminogen
(metabolism, physiology)
- Plasminogen Activators
(metabolism)
- Time Factors
- Urokinase-Type Plasminogen Activator
(physiology)
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