Proteoglycan degrading activity in granulomatous inflammation: Comparison between the C57bl/6 and C57bg/bg mouse
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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.
15 animals (female C57bl/6 and C57bg/bg mice) per group were used.
Cotton-wrapped rat femoral head cartilages were implanted subcutaneously into the dorsum of the mice and the granulomas excised fourteen days later.
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.
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.
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 C57bl/6 and C57bg/bg.
Key wordsCartilage degradation model Beige mouse Proteoglycan Cathepsin G Elastase
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