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The plasminogen activator/plasmin system is essential for development of the joint inflammatory phase of collagen type II-induced arthritis

Li, JN; Ny, A; Leonardsson, G; Nandakumar, KS; Holmdahl, Rikard LU and Ny, T (2005) In American Journal of Pathology 166(3). p.783-792
Abstract
The plasminogen activator (PA) system has been proposed to have important roles in rheumatoid arthritis. Here we have used the autoinumme 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 wildtype 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 CH immunization as well as the binding of labeled anti-CII antibodies to the surface of cartilage were... (More)
The plasminogen activator (PA) system has been proposed to have important roles in rheumatoid arthritis. Here we have used the autoinumme 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 wildtype 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 CH 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 CH. 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. (Less)
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organization
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Contribution to journal
publication status
published
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in
American Journal of Pathology
volume
166
issue
3
pages
783 - 792
publisher
American Society for Investigative Pathology
external identifiers
  • pmid:15743790
  • wos:000227288300015
  • scopus:14644424644
ISSN
1525-2191
language
English
LU publication?
yes
id
3e01b0e3-7ee1-4e91-b446-f1e8c33a8583 (old id 252164)
alternative location
http://ajp.amjpathol.org/cgi/content/abstract/166/3/783
date added to LUP
2007-09-28 13:33:54
date last changed
2017-03-19 03:35:21
@article{3e01b0e3-7ee1-4e91-b446-f1e8c33a8583,
  abstract     = {The plasminogen activator (PA) system has been proposed to have important roles in rheumatoid arthritis. Here we have used the autoinumme 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 wildtype 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 CH 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 CH. 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.},
  author       = {Li, JN and Ny, A and Leonardsson, G and Nandakumar, KS and Holmdahl, Rikard and Ny, T},
  issn         = {1525-2191},
  language     = {eng},
  number       = {3},
  pages        = {783--792},
  publisher    = {American Society for Investigative Pathology},
  series       = {American Journal of Pathology},
  title        = {The plasminogen activator/plasmin system is essential for development of the joint inflammatory phase of collagen type II-induced arthritis},
  volume       = {166},
  year         = {2005},
}