Role of the tissue factor pathway in synovial inflammation

Détails

ID Serval
serval:BIB_889BC6BA6B0F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Role of the tissue factor pathway in synovial inflammation
Périodique
Arthritis and Rheumatism
Auteur(s)
Busso  N., Morard  C., Salvi  R., Peclat  V., So  A.
ISSN
0004-3591 (Print)
Statut éditorial
Publié
Date de publication
03/2003
Volume
48
Numéro
3
Pages
651-9
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Mar
Résumé
OBJECTIVE: Clinical and experimental evidence suggests that extravascular fibrin deposition in arthritic joints is prominent and deleterious. The aim of this study was to investigate the contributions of tissue factor (TF) and its inhibitor, TF pathway inhibitor (TFPI), in arthritis. METHODS: Synovial tissue specimens obtained from 10 patients with rheumatoid arthritis (RA) and 12 patients with osteoarthritis (OA) were scored histologically for inflammation and fibrin content. TF and TFPI levels were assayed at antigenic and functional levels. TF messenger RNA (mRNA) levels were determined using RNase protection assays. The effect of TF inhibition in murine antigen-induced arthritis (AIA) was assessed by administering systemically active site-blocked activated factor VIIa (FVIIai). RESULTS: Functional TF activity was significantly increased in synovial membranes from RA patients compared with those from OA patients. In contrast, no difference in TF mRNA and TF antigenic levels was observed between these 2 groups. This discrepancy can be accounted for by TFPI, because we observed a negative correlation between TF activity and TFPI activity. There was a significant difference between the RA and OA groups in terms of synovial inflammation, with more inflammation observed in the RA group. Most importantly, TF activity was associated with fibrin (P = 0.024) and with histologic inflammation (P = 0.03) scores. In AIA, inhibition of TF-induced coagulation by FVIIai led, on day 9 of arthritis, to decreased synovial thickness and decreased articular cartilage damage, although only the latter difference between controls and treated mice reached significance (P < 0.04). Finally, in FVIIai-treated mice, there was a strong negative association between the prothrombin time and intraarticular fibrin deposition. CONCLUSION: Our results show that TF expression in arthritic synovial tissue favors extravascular coagulation and may play a role in inflammation in RA. In this context, TF inhibitors may be of therapeutic value.
Mots-clé
Aged Animals Arthritis, Experimental/prevention & control Arthritis, Rheumatoid/*metabolism/pathology Dansyl Compounds/therapeutic use Disease Models, Animal Factor VIIa/therapeutic use Female Fibrin/metabolism Fibrinolytic Agents/*metabolism/pharmacology Hindlimb/metabolism/pathology/radionuclide imaging Humans Immunohistochemistry Lipoproteins/genetics/*metabolism/pharmacology Male Mice Mice, Inbred C57BL Middle Aged Osteoarthritis/*metabolism/pathology RNA, Messenger/metabolism Synovitis/*metabolism/pathology Thromboplastin/genetics/*metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/01/2008 9:39
Dernière modification de la notice
20/08/2019 15:47
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