Plasminogen activator inhibitor type-1 deficiency attenuates murine antigen-induced arthritis
Details
Serval ID
serval:BIB_CAEAAA162872
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Plasminogen activator inhibitor type-1 deficiency attenuates murine antigen-induced arthritis
Journal
Rheumatology
ISSN
1462-0324 (Print)
Publication state
Published
Issued date
02/2002
Volume
41
Number
2
Pages
136-41
Notes
Journal Article --- Old month value: Feb
Abstract
OBJECTIVE: To examine the role of plasminogen activator inhibitor type-1 (PAI-1), the major fibrinolytic inhibitor, in vivo during murine antigen-induced arthritis (AIA). METHODS: AIA was induced in PAI-1-deficient mice and control wild-type mice. Arthritis severity was evaluated by technetium 99m (99mTc) uptake in the knee joints and by histological scoring. Intra-articular fibrin deposition was examined by immunohistochemistry and synovial fibrinolysis quantitated by tissue D-dimer measurements and zymograms. RESULTS: Joint inflammation, quantitated by 99mTc uptake, was significantly reduced in PAI-1(-/-) mice on day 7 after arthritis onset (P<0.01). Likewise, synovial inflammation, evaluated by histological scoring, was significantly decreased in PAI-1-deficient mice on day 10 after arthritis onset (P<0.001). Articular cartilage damage was significantly decreased in PAI-1(-/-) mice, as shown by histological grading of safranin-O staining on day 10 after arthritis onset (P<0.005). Significantly decreased synovial accumulation of fibrin was observed by day 10 in arthritic joints of PAI-1(-/-) mice (P<0.005). Accordingly, the synovial tissue content of D-dimers, the specific fibrin degradation products generated by plasmin, were increased in PAI-1(-/-) mice (P<0.02). Finally, as expected, PA activity was increased in synovial tissues from PAI-1(-/-) mice, as shown by zymographic analysis. CONCLUSIONS: These results indicate that deficiency of PAI-1 results in increased synovial fibrinolysis, leading to reduced fibrin accumulation in arthritic joints and reduced severity of AIA.
Keywords
Animals
Antigens/immunology
Arthritis, Rheumatoid/*immunology/metabolism/*pathology
Disease Models, Animal
Fibrin/metabolism
Fibrinolysis/immunology
Knee Joint/immunology/metabolism/pathology
Mice
Mice, Inbred C57BL
Mice, Knockout
Plasminogen Activator Inhibitor 1/*genetics/immunology
Synovial Membrane/immunology/metabolism/pathology
Technetium/diagnostic use/pharmacokinetics
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 9:38
Last modification date
20/08/2019 16:45