Tissue-type plasminogen activator deficiency exacerbates arthritis

YH Yang, P Carmeliet, JA Hamilton - The Journal of Immunology, 2001 - journals.aai.org
YH Yang, P Carmeliet, JA Hamilton
The Journal of Immunology, 2001journals.aai.org
Fibrin deposition, cell migration, and tissue remodeling are key components in the lesions of
inflammatory joint diseases, such as rheumatoid arthritis. The plasminogen activators (PAs),
namely, tissue-type PA (t-PA) and urokinase PA, are implicated in these aspects of an
inflammatory response, although their precise roles are yet to be defined. We therefore used
gene-deficient mice to explore their role in a two-stage arthritis model involving intraarticular
methylated BSA injection, followed by systemic IL-1 treatment. We report in this study that …
Abstract
Fibrin deposition, cell migration, and tissue remodeling are key components in the lesions of inflammatory joint diseases, such as rheumatoid arthritis. The plasminogen activators (PAs), namely, tissue-type PA (t-PA) and urokinase PA, are implicated in these aspects of an inflammatory response, although their precise roles are yet to be defined. We therefore used gene-deficient mice to explore their role in a two-stage arthritis model involving intraarticular methylated BSA injection, followed by systemic IL-1 treatment. We report in this study that both t-PA and urokinase PA are protective for the mild arthritis induced by intraarticular methylated BSA injection alone, since absence of either of them exacerbates the response; following sc IL-1 injection, t-PA−/− mice had particularly severe disease. Fibrin deposition appeared to parallel disease severity under the various conditions, suggesting that PA-mediated fibrinolysis may be normally playing a protective role in inflammatory joint disease.
journals.aai.org