PROTEOGLYCAN DEGRADING ACTIVITY IN GRANULOMATOUS INFLAMMATION - COMPARISON BETWEEN THE C57BL 6 AND C57BG/BG MOUSE/

Objective and Design: Proteoglycan (GAG) and collagen are lost from ca rtilage juxtaposed to murine granulomatous tissue in both control and C57bg/bg (elastase deficient mice). The objective was to extract and c haracterise 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 gra nulomas excised fourteen days later. Methods: Granuloma and granuloma cell-granule preparations were fractionated within a detergent-based b uffer 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 correla ted 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 cathep sin 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 i n the murine cotton-pellet granuloma in both C57b1/6 and C57bg/bg.