Cathepsins B and L in synovial fluids from patients with rheumatoid arthritis and the effect of cathepsin B on the activation of pro-urokinase

J Med Invest. 2000 Feb;47(1-2):61-75.


To clarify the pathophysiological role of cathepsins in rheumatoid arthritis (RA), we investigated whether cathepsin B or cathepsin L was increased in synovial fluid (SF) of RA joints, and whether the cathepsin isolated from SF of RA patients activated pro-urokinase or not. Thus, we estimated the content of cathepsins in SF of RA patients by measuring their activities by fluorospectrometry, using Z-Phe-Arg-MCA as the substrate. Cathepsin activity was approximately 4-fold higher in the SF of RA patients than in those of patients with osteoarthritis. Cathepsin B and cathepsin L were separated by cation-exchange column chromatography. As a result, a large peak corresponding to cathepsin B and a very small peak corresponding to cathepsin L were detected. Biochemical sequential fractionation of the cathepsin purified from the SF showed that the large peak was mainly composed of cathepsin B. This purified enzyme induced conversion of pro-urokinase to urokinase, and the Km for pro-urokinase was approximately 8.27 microM. These findings indicated that an imbalance between cathepsin B and its inhibitors occurred due to increased concentrations of active cathepsin B in RA articular lesions, and that cathepsin B might be related to the degradation of cartilage in RA by activating the fibrinolytic cascade.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Arthritis, Rheumatoid / enzymology*
  • Cathepsin B / antagonists & inhibitors
  • Cathepsin B / isolation & purification
  • Cathepsin B / metabolism*
  • Cathepsin B / pharmacology
  • Cathepsin L
  • Cathepsins / metabolism*
  • Cysteine Endopeptidases
  • Cysteine Proteinase Inhibitors / pharmacology
  • Dipeptides / pharmacology
  • Endopeptidases*
  • Enzyme Activation
  • Enzyme Precursors / metabolism*
  • Female
  • Humans
  • Leucine / analogs & derivatives
  • Leucine / pharmacology
  • Liver / enzymology
  • Male
  • Middle Aged
  • Osteoarthritis / enzymology
  • Recombinant Proteins / metabolism
  • Synovial Fluid / enzymology*
  • Urokinase-Type Plasminogen Activator / metabolism*


  • Cysteine Proteinase Inhibitors
  • Dipeptides
  • Enzyme Precursors
  • Recombinant Proteins
  • N-(3-propylcarbamoyloxirane-2-carbonyl)-isoleucyl-proline
  • Cathepsins
  • Endopeptidases
  • Urokinase-Type Plasminogen Activator
  • Cysteine Endopeptidases
  • Cathepsin B
  • CTSL protein, human
  • Cathepsin L
  • Leucine
  • E 64
  • saruplase