Yang Y H, Carmeliet P, Hamilton J A
Department of Medicine, Arthritis and Inflammation Research Centre, University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
J Immunol. 2001 Jul 15;167(2):1047-52. doi: 10.4049/jimmunol.167.2.1047.
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.
纤维蛋白沉积、细胞迁移和组织重塑是类风湿关节炎等炎性关节疾病病变的关键组成部分。纤溶酶原激活剂（PAs），即组织型PA（t-PA）和尿激酶型PA，参与了炎症反应的这些方面，尽管它们的确切作用尚待确定。因此，我们使用基因缺陷小鼠在一个两阶段关节炎模型中探索它们的作用，该模型包括关节内注射甲基化牛血清白蛋白，随后进行全身性白细胞介素-1治疗。我们在本研究中报告，t-PA和尿激酶型PA对单独关节内注射甲基化牛血清白蛋白诱导的轻度关节炎均具有保护作用，因为缺失其中任何一种都会加剧反应；皮下注射白细胞介素-1后，t-PA（-/-）小鼠的病情特别严重。在各种条件下，纤维蛋白沉积似乎与疾病严重程度平行，这表明PA介导的纤维蛋白溶解可能通常在炎性关节疾病中发挥保护作用。
