Cathepsin G: the significance in rheumatoid arthritis as a monocyte chemoattractant.
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.
Miyata
Junya
J
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, ssone@clin.med.tokushima-u.ac.jp.
Tani
Kenji
K
Sato
Keiko
K
Otsuka
Shinsaku
S
Urata
Tomoyuki
T
Lkhagvaa
Battur
B
Furukawa
Chiyuki
C
Sano
Nobuya
N
Sone
Saburo
S
D001172:Arthritis, Rheumatoid / Q000276:immunology*; D056649:Cathepsin G; D002403:Cathepsins / Q000378:metabolism*; D002630:Chemotactic Factors / Q000276:immunology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D008264:Macrophages; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology*; D012697:Serine Endopeptidases / Q000378:metabolism*; D013582:Synovial Fluid / Q000737:chemistry / Q000276:immunology; D013583:Synovial Membrane / Q000737:chemistry / Q000276:immunology
D002630:Chemotactic Factors; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G