Miyata Junya, Tani Kenji, Sato Keiko, Otsuka Shinsaku, Urata Tomoyuki, Lkhagvaa Battur, Furukawa Chiyuki, Sano Nobuya, Sone Saburo
Department of Internal Medicine and Molecular Therapeutics, Institute of Health Biosciences, The University of Tokushima Graduate School, 18-15 Kuramoto-cho 3, Tokushima, 770-8503, Japan,
Rheumatol Int. 2007 Feb;27(4):375-82. doi: 10.1007/s00296-006-0210-8. Epub 2006 Sep 15.
Human cathepsin G (EC 3.4.21.20) has been reported to have the in vitro chemotactic activity for human monocytes. In this study, we examined the role of cathepsin G in monocyte involvement in joint inflammation of rheumatoid arthritis (RA) as a monocyte chemoattractant. Eighteen patients with RA and four patients with osteoarthritis (OA) were used in this study. Thiobenzylester substrate, Succ-Phe-Leu-Phe-S-Bzl, was used to measure the activity of cathepsin G in synovial fluids. Monocyte migration induced by cathepsin G and synovial fluids was assessed by a 48-well microchemotaxis chamber technique. Immunohistochemical staining was performed to determine the cellular origin of cathepsin G in RA synovial tissue. A very low activity of cathepsin G was detected in synovial fluids from patients with OA. On the other hand, significantly increased activity of cathepsin G was detected in patients with RA when compared with the value of OA patients. A considerable monocyte chemotactic activity was detected in the synovial fluid of RA patients, and the activity was partially decreased by the treatment with inhibitors for cathepsin G, alpha1-antichymotrypsin and phenylmethylsulfonyl fluoride. The activity of cathepsin G was significantly correlated with the neutrophil counts in synovial fluids and the concentration of interleukin-6. Immunohistochemical studies showed that cathepsin G was strongly expressed by synovial lining cells, and weakly expressed by macrophages and neutrophils in synovial tissues. This study indicates that the monocyte chemotactic activity of cathepsin G may have a role in the pathogenesis of RA synovial inflammation.
据报道，人组织蛋白酶G（EC 3.4.21.20）对人单核细胞具有体外趋化活性。在本研究中，我们研究了组织蛋白酶G作为单核细胞趋化因子在类风湿性关节炎（RA）关节炎症中单核细胞参与过程中的作用。本研究使用了18例RA患者和4例骨关节炎（OA）患者。硫代苄酯底物Succ-Phe-Leu-Phe-S-Bzl用于测量滑液中组织蛋白酶G的活性。通过48孔微量趋化室技术评估组织蛋白酶G和滑液诱导的单核细胞迁移。进行免疫组织化学染色以确定RA滑膜组织中组织蛋白酶G的细胞来源。在OA患者的滑液中检测到非常低的组织蛋白酶G活性。另一方面，与OA患者的值相比，在RA患者中检测到组织蛋白酶G的活性显著增加。在RA患者的滑液中检测到相当大的单核细胞趋化活性，并且用组织蛋白酶G抑制剂、α1-抗糜蛋白酶和苯甲基磺酰氟处理后该活性部分降低。组织蛋白酶G的活性与滑液中的中性粒细胞计数和白细胞介素-6的浓度显著相关。免疫组织化学研究表明，滑膜衬里细胞强烈表达组织蛋白酶G，滑膜组织中的巨噬细胞和中性粒细胞弱表达。本研究表明，组织蛋白酶G的单核细胞趋化活性可能在RA滑膜炎症的发病机制中起作用。
