Plant proteinase inhibitor from enterolobium contortisiliquum (EcTI ) attenuates elastase-induced pulmonary inflammatory and remodeling alterations in mice

Aims: To evaluate if a plant Kunitz proteinase inhibitor EcTI contributes to inactivation of elastase-induced mechanical, inflammatory and extracellular matrix remodelling alterations. Methods: C57Bl6 mice received elastase (50ml/animal- IN-E group). Control group received saline (Ve group). Mice were treated with EcTI (2mg/kg) at days 1, 7, 14, 21, 28 and 35 after elastase instillation (I-E group). At day 40, mice were anesthetized, mechanically ventilated and we analyzed respiratory system resistance and elastance, tissue elastance, tissue damping, and airway resistance. Afterwards, BAL was performed and lungs were removed. By morphometry, we quantified the mean linear intercept (Lm), collagen and elastic fibers in distal lung. Results: There were no differences in pulmonary mechanics comparing all groups. In E-group, there was an increase in BAL-total cells, BAL-lymphocytes, BAL-neutrophils, collagen, elastic fibers and LM compared to control (p<0.05). In I-E group, EcTi attenuated the increase in BAL-total cells (65.2±3.3×10 4 cells/mL) and BAL-neutrophils (1.3±0.7×10 4 cells/mL) compared to E-group (respectively: 110.7±9.7×10 4 cells/mL and 8.0±1.4×10 4 cells/mL, p<0.05). There was a decrease in the collagen content in I-E group (43.2±4.3%) compared to E-group (59%±2.5, p<0.05). Conclusions: This proteinase inhibitor ( EcTI ) reduced 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 HCFMUSP.