The plasminogen activator/plasmin system is essential for development of the joint inflammatory phase of collagen type II-induced arthritis
(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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https://lup.lub.lu.se/record/252164
- author
- Li, JN ; Ny, A ; Leonardsson, G ; Nandakumar, KS ; Holmdahl, Rikard LU and Ny, T
- organization
- publishing date
- 2005
- type
- Contribution to journal
- publication status
- published
- subject
- 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
- 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
- 3e01b0e3-7ee1-4e91-b446-f1e8c33a8583 (old id 252164)
- alternative location
- http://ajp.amjpathol.org/cgi/content/abstract/166/3/783
- date added to LUP
- 2016-04-01 12:20:37
- date last changed
- 2022-01-27 02:18:51
@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}},
url = {{http://ajp.amjpathol.org/cgi/content/abstract/166/3/783}},
volume = {{166}},
year = {{2005}},
}