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Effects of pronase on granuloma angiogenesis and granulation tissue formation were investigated using granuloma pouches induced by Freund's complete adjuvant containing 0.1% croton oil in normal and alloxan diabetic mice. Granuloma angiogenesis was measured by the carmine dye infusion method. Pronase (2 mg/kg/day) was daily injected into the pouch for 3 to 7 days, and its effects were compared with those of hydrocortisone (1 mg/kg/day) and indomethacin (2 mg/kg/day). Pronase significantly inhibited the wet weight of pouch granuloma, mainly in the later stage of inflammation in normal mice. But it failed to decrease both the content of hydroxyproline in granuloma and the amount of carmine dye infused into the newly developed capillaries, whereas hydrocortisone and indomethacin significantly decreased them. In pathohistological findings, pronase increased angiogenesis and subsequently enhanced the repair rate by a dense arrangement of mature connective tissue, although hydrocortisone and indomethacin markedly decreased angiogenesis. In alloxan diabetic mice, granulation tissue was significantly produced less than that in normal mice. Hydrocortisone potentiated the decrease in granulation tissue formation of diabetic mice, whereas pronase did not markedly affect on it. The ratios of the amount of capillaries to the wet weight of granuloma tissue in pronase-treated mice were higher than those of control mice. Pronase was concluded to enhance angiogenesis in granuloma tissue in addition to the activation of collagenolysis and proteolysis.

Mechanism of action of pronase on chronic proliferative inflammation including granuloma angiogenesis in mice.