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类风湿性关节炎滑膜中的组织蛋白酶B及其内源性抑制剂胱抑素C

Cathepsin B and its endogenous inhibitor cystatin C in rheumatoid arthritis synovium.

作者信息

Hansen T, Petrow P K, Gaumann A, Keyszer G M, Eysel P, Eckardt A, Bräuer R, Kriegsmann J

机构信息

Institute of Pathology and the Clinic of Orthopedics, University of Mainz, Germany.

出版信息

J Rheumatol. 2000 Apr;27(4):859-65.

PMID:10782807
Abstract

OBJECTIVE

To compare the expression of cathepsin B and its endogenous inhibitor cystatin C in synovial tissue of patients with rheumatoid arthritis (RA) and to determine the cell type expressing cystatin C.

METHODS

The expression of cathepsin B and cystatin C was studied by immunohistochemistry in synovial tissue of 10 patients with RA and compared to healthy controls. Applying double labeling methods, the expression of cathepsin B was compared to that of cystatin C. To determine the cell type expressing cystatin C, double labeling with anti-CD68 (PG-M1) was performed.

RESULTS

Both cystatin C and cathepsin B were strongly expressed in synoviocytes of patients with RA. Furthermore, fibroproliferative tissue at the site of cartilage and bone destruction contained fibroblast-like and macrophage-like cells positive for cystatin C and cathepsin B, whereas normal synovial tissue exhibited only limited expression of these molecules. Osteoclasts revealed positive staining for CD68 and cystatin C, but not for cathepsin B.

CONCLUSION

Cystatin C is a product of both macrophage-like and fibroblast-like synoviocytes. The strong expression of both the matrix degrading cysteine proteinase cathepsin B and the cysteine proteinase inhibitor cystatin C in rheumatoid synovium, particularly at the sites of bone and cartilage erosion, suggests that cystatin C--although increased--is not sufficient to prevent matrix degradation by cathepsin B.

摘要

目的

比较类风湿关节炎(RA)患者滑膜组织中组织蛋白酶B及其内源性抑制剂胱抑素C的表达,并确定表达胱抑素C的细胞类型。

方法

采用免疫组织化学方法研究10例RA患者滑膜组织中组织蛋白酶B和胱抑素C的表达,并与健康对照进行比较。应用双重标记方法,比较组织蛋白酶B与胱抑素C的表达。为确定表达胱抑素C的细胞类型,进行抗CD68(PG-M1)双重标记。

结果

胱抑素C和组织蛋白酶B在RA患者的滑膜细胞中均强烈表达。此外,软骨和骨破坏部位的纤维增生组织中含有胱抑素C和组织蛋白酶B阳性的成纤维细胞样和巨噬细胞样细胞,而正常滑膜组织中这些分子的表达有限。破骨细胞CD68和胱抑素C染色阳性,但组织蛋白酶B染色阴性。

结论

胱抑素C是巨噬细胞样和成纤维细胞样滑膜细胞的产物。基质降解性半胱氨酸蛋白酶组织蛋白酶B和半胱氨酸蛋白酶抑制剂胱抑素C在类风湿滑膜中均强烈表达,尤其是在骨和软骨侵蚀部位,这表明胱抑素C虽然增加,但不足以阻止组织蛋白酶B对基质的降解。

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