title: Tissue-type plasminogen activator deficiency exacerbates arthritis.
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 s.c. 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.
authors: Department of Medicine, Arthritis and Inflammation Research Centre, University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia. yuan.yang@med.monash.edu.au
authors: Y H
authors: YH
authors: Yang
authors: P
authors: P
authors: Carmeliet
authors: J A
authors: JA
authors: Hamilton
mesh_terms: D000818:Animals; D001168:Arthritis / Q000201:enzymology* / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D002452:Cell Count; D005340:Fibrinogen / Q000378:metabolism; D007270:Injections, Intra-Articular; D007375:Interleukin-1 / Q000008:administration & dosage; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012710:Serum Albumin, Bovine / Q000008:administration & dosage; D012720:Severity of Illness Index; D010959:Tissue Plasminogen Activator / Q000172:deficiency* / Q000235:genetics*; D014568:Urokinase-Type Plasminogen Activator / Q000172:deficiency / Q000235:genetics
chemical_list: D007375:Interleukin-1; C029180:methylated bovine serum albumin; D012710:Serum Albumin, Bovine; D005340:Fibrinogen; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator