Proteoglycan degrading activity in granulomatous inflammation: comparison between the C57b1/6 and C57bg/bg mouse

Abstract

Objective and design: Proteoglycan (GAG) and collagen are lost from cartilage juxtaposed to murine granulomatous tissue in both control and C57bg/bg (elastase deficient mice). The objective was to extract and characterise proteoglycan degrading activity within granulomas of both strains.

Materials: 15 animals (female C57b1/6 and C57bg/bg mice) per group were used.

Treatment: Cotton-wrapped rat femoral head cartilages were implanted subcutaneously into the dorsum of the mice and the granulomas excised fourteen days later.

Methods: Granuloma and granuloma cell-granule preparations were fractionated within a detergent-based buffer and tested for their abilities to degrade cartilage in vitro in the presence and absence of enzyme inhibitors. Elastase and cathepsin G activities were also assessed using specific substrates. Statistical significance was calculated using Student's t-test.

Results: Extracts from both strains induced the loss of cartilage GAG. This was correlated with cathepsin G activity (r = 0.96) and was inhibited by a specific cathepsin-G inhibitor (95%, p < 0.001), but not specific elastase or metalloproteinase inhibitors. Elastase activity but not that of cathepsin G was absent in the beige mice, whilst both enzymes were active in the controls.

Conclusions: It appears that neutrophil cathepsin G may play an important role in the degradation of cartilage proteoglycan in the murine cotton-pellet granuloma in both C57b1/6 and C57bg/bg.