Shin H, Nakajima T, Kitajima I, Shigeta K, Abeyama K, Imamura T, Okano T, Kawahara K, Nakamura T, Maruyama I
Department of Clinical Laboratory Medicine, School of Medicine, Kagoshima University, Japan.
Clin Immunol Immunopathol. 1995 Sep;76(3 Pt 1):225-33. doi: 10.1006/clin.1995.1120.
Synovial cell proliferation is one of the pathological bases of rheumatoid arthritis (RA). Several cytokines including IL-1 and IL-6 and growth factors have been shown to be involved in the synovial cell proliferation in RA. Thrombin is a multifunctional protease and acts as a mitogen for several cell types through its specific receptor. To assess whether thrombin is involved in overproliferation of rheumatoid synovial cells, we measured the concentration of thrombin-anti-thrombin III (ATIII) complex (TAT) in synovial fluid obtained from patients with RA or osteoarthritis (OA). We also examined the effect of thrombin or thrombin receptor agonist peptide (TRAP) on cell growth of synovial cell clones (SCCs) established from an RA patient. The concentrations of TAT in the synovial fluid from patients with RA were significantly higher than in those with OA. Moreover, both thrombin and TRAP enhanced proliferation of synovial cells in vitro. We also characterized the expression of thrombin receptor mRNA by reverse transcription-PCR. The expression of mRNA for thrombin receptor was up-regulated by thrombin or TRAP stimulation. Thrombin receptor antigen was also detected on both SCCs and synovial tissue from RA patients by immunostaining using a monoclonal antibody against thrombin receptor. These findings indicate that thrombin may act as a mitogen for synovial cells through thrombin receptor and may play some role in synovial overproliferation and remodeling in RA.
滑膜细胞增殖是类风湿关节炎（RA）的病理基础之一。包括白细胞介素 -1（IL -1）和白细胞介素 -6（IL -6）在内的多种细胞因子以及生长因子已被证明与RA中的滑膜细胞增殖有关。凝血酶是一种多功能蛋白酶，通过其特异性受体对多种细胞类型起促有丝分裂原的作用。为了评估凝血酶是否参与类风湿滑膜细胞的过度增殖，我们测量了从RA患者或骨关节炎（OA）患者获得的滑液中凝血酶 - 抗凝血酶III（ATIII）复合物（TAT）的浓度。我们还研究了凝血酶或凝血酶受体激动肽（TRAP）对从一名RA患者建立的滑膜细胞克隆（SCCs）细胞生长的影响。RA患者滑液中TAT的浓度显著高于OA患者。此外，凝血酶和TRAP均能增强体外滑膜细胞的增殖。我们还通过逆转录 - 聚合酶链反应（RT - PCR）对凝血酶受体mRNA的表达进行了表征。凝血酶受体mRNA的表达在凝血酶或TRAP刺激下上调。使用抗凝血酶受体单克隆抗体通过免疫染色在RA患者的SCCs和滑膜组织上也检测到了凝血酶受体抗原。这些发现表明，凝血酶可能通过凝血酶受体作为滑膜细胞的促有丝分裂原，并可能在RA的滑膜过度增殖和重塑中发挥一定作用。
