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Contrasting roles of plasminogen deficiency in different rheumatoid arthritis models

Li, J N ; Guo, Y Z ; Holmdahl, Rikard LU and Ny, T (2005) In Arthritis and Rheumatism 52(8). p.2541-2548
Abstract
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 11 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 CH immunization alone, wild-type mice developed arthritis in... (More)
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 11 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 CH 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 CH 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 CH 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. (Less)
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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Arthritis and Rheumatism
volume
52
issue
8
pages
2541 - 2548
publisher
John Wiley & Sons Inc.
external identifiers
  • wos:000231078800042
  • pmid:16052596
  • scopus:23644459509
ISSN
1529-0131
DOI
10.1002/art.21229
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Medical Inflammation Research (013212019)
id
aa2fe282-2f9b-4fa1-8779-51d9552a6f86 (old id 229410)
date added to LUP
2016-04-01 11:47:37
date last changed
2022-01-26 18:19:00
@article{aa2fe282-2f9b-4fa1-8779-51d9552a6f86,
  abstract     = {{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 11 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 CH 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 CH 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 CH 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.}},
  author       = {{Li, J N and Guo, Y Z and Holmdahl, Rikard and Ny, T}},
  issn         = {{1529-0131}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{2541--2548}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Arthritis and Rheumatism}},
  title        = {{Contrasting roles of plasminogen deficiency in different rheumatoid arthritis models}},
  url          = {{http://dx.doi.org/10.1002/art.21229}},
  doi          = {{10.1002/art.21229}},
  volume       = {{52}},
  year         = {{2005}},
}