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Cathepsin G: the significance in rheumatoid arthritis as a monocyte chemoattractant

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Abstract

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, α1-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.

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Acknowledgments

We thank Ms. Tomoko Oka for assistance with monocyte preparation. This work was supported in part by a Grant-in-Aid for General Scientific Research (B) from the Ministry of Education, Science and Culture and the Ministry of Health and Welfare of Japan.

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Authors and Affiliations

  1. 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

    Junya Miyata, Kenji Tani, Keiko Sato, Shinsaku Otsuka, Tomoyuki Urata, Battur Lkhagvaa, Chiyuki Furukawa & Saburo Sone

  2. Department of Pathology, Tokushima University Hospital, Tokushima, Japan

    Nobuya Sano

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  1. Junya Miyata
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Correspondence to Saburo Sone.

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Miyata, J., Tani, K., Sato, K. et al. Cathepsin G: the significance in rheumatoid arthritis as a monocyte chemoattractant. Rheumatol Int 27, 375–382 (2007). https://doi.org/10.1007/s00296-006-0210-8

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  • DOI: https://doi.org/10.1007/s00296-006-0210-8

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