Plasminogen activator inhibitor type-1 deficiency attenuates murine antigen-induced arthritis

Détails

ID Serval
serval:BIB_CAEAAA162872
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Plasminogen activator inhibitor type-1 deficiency attenuates murine antigen-induced arthritis
Périodique
Rheumatology
Auteur(s)
Van Ness  K., Chobaz-Peclat  V., Castellucci  M., So  A., Busso  N.
ISSN
1462-0324 (Print)
Statut éditorial
Publié
Date de publication
02/2002
Volume
41
Numéro
2
Pages
136-41
Notes
Journal Article --- Old month value: Feb
Résumé
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.
Mots-clé
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
Oui
Création de la notice
25/01/2008 9:38
Dernière modification de la notice
09/05/2019 1:16
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