Cathepsin G: the significance in rheumatoid arthritis as a monocyte chemoattractant
Cathepsin G: the significance in rheumatoid arthritis as a monocyte chemoattractant
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DOI：
10.1007/s00296-006-0210-8
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发表时间：
2007-02-01
影响因子：
4
通讯作者：
Sone, Saburo
中科院分区：
文献类型：
--
作者：
Miyata, Junya;Tani, Kenji;Sone, Saburo
已报道人组织蛋白酶G（EC 3.4.21.20）对人单核细胞具有体外趋化活性。在这项研究中，我们研究了组织蛋白酶G的作用，单核细胞参与类风湿关节炎（RA）的关节炎症作为单核细胞趋化剂。18例RA患者和4例骨关节炎（OA）患者用于本研究。硫代苄基酯底物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。免疫组织化学染色，以确定RA滑膜组织中的组织蛋白酶G的细胞来源。OA患者滑液中检测到极低活性的组织蛋白酶G。另一方面，组织蛋白酶G的活性显着增加时，检测到RA患者与OA患者的值相比。在RA患者的滑液中检测到相当大的单核细胞趋化活性，并且通过用组织蛋白酶G、α 1-抗糜蛋白酶和苯甲基磺酰氟的抑制剂治疗，该活性部分降低。组织蛋白酶G活性与关节液中性粒细胞计数和白细胞介素6浓度呈显著相关。免疫组化结果显示组织蛋白酶G在滑膜衬里细胞中呈强表达，在滑膜组织中的巨噬细胞和中性粒细胞中呈弱表达。本研究提示组织蛋白酶G的单核细胞趋化活性可能在类风湿关节炎滑膜炎症的发病机制中起作用。
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, alpha 1-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.