Plant proteinase inhibitor from crataeva tapia (CrataBl) attenuates inflammation and remodelling induced by elastase in mice

Aims: To evaluate if a plant Kunitz proteinase inhibitor CrataBl modulates inflammatory remodelling alterations induced by elastase. Methods: C57Bl6 mice received elastase intratracheal (50μl/animal group) or saline (Ve group). Afterwards, mice were treated with CrataBl (2mg/kg) on days 1, 14, 21 after elastase instillation (I-E group) or saline instillation. On day 30 mice were anesthetized and mechanically ventilated. Afterwards, lungs were removed en bloc. By morphometry, we quantified the amount of neutrophils and positive cells for MMP-9, MMP-12 and MAC-2 in distal lung parenchyma. Results: In elastase group there was a significant increase in neutrophils, MMP-9, MMP-12, TNF-α and MAC-2 compared to controls (p<0.05). The CrataBl treatment of elastase group (I-E group) decreased the amount of neutrophils (7.40±0.32/10 4 μm 2 ), the amount of the positive cells for MMP-9 (10.35±0.65/10 4 μm 2 ), MMP-12 (14.15±0.59/10 4 μm 2 ) and for MAC-2 (8.40±0.80/10 4 μm 2 ) compared to E-group (p<0.05). Conclusions: This Kunitz proteinase inhibitor (CrataBl) attenuated elastase-induced pulmonary inflammatory and extracellular matrix remodeling alterations induced by elastase. Although more studies need to be performed, this inhibitor may contribute as potential therapeutic tool for COPD management. Financial Support: FAPESP, CNPq, LIM-20-HC-FMUSP.