Plant Proteinase Inhibitor BbCI Modulates Lung Inflammatory Responses and Mechanic and Remodeling Alterations Induced by Elastase in Mice.

Osmar A Theodoro-Junior,Ariana C Florencio,Bruno T M Oliveira,Carla M Prado,Edna A Leick,Marlon V Brito,Rafael Almeida-Reis,Mílton A Martins,Caroline A Owen,Maria L V Oliva,Alessandra C Toledo-Arruda,Camila R Bonturi,Fernanda D T Q S Lopes,Leandro V Oliva,Iolanda F L C Tibério

doi:10.1155/2017/8287125

Abstract

Background. Proteinases play a key role in emphysema. Bauhinia bauhinioides cruzipain inhibitor (BbCI) is a serine-cysteine proteinase inhibitor. We evaluated BbCI treatment in elastase-induced pulmonary alterations. Methods. C57BL/6 mice received intratracheal elastase (ELA group) or saline (SAL group). One group of mice was treated with BbCI (days 1, 15, and 21 after elastase instillation, ELABC group). Controls received saline and BbCI (SALBC group). After 28 days, we evaluated respiratory mechanics, exhaled nitric oxide, and bronchoalveolar lavage fluid. In lung tissue we measured airspace enlargement, quantified neutrophils, TNFα-, MMP-9-, MMP-12-, TIMP-1-, iNOS-, and eNOS-positive cells, 8-iso-PGF2α, collagen, and elastic fibers in alveolar septa and airways. MUC-5-positive cells were quantified only in airways. Results. BbCI reduced elastase-induced changes in pulmonary mechanics, airspace enlargement and elastase-induced increases in total cells, and neutrophils in BALF. BbCI reduced macrophages and neutrophils positive cells in alveolar septa and neutrophils and TNFα-positive cells in airways. BbCI attenuated elastic and collagen fibers, MMP-9- and MMP-12-positive cells, and isoprostane and iNOS-positive cells in alveolar septa and airways. BbCI reduced MUC5ac-positive cells in airways. Conclusions. BbCI improved lung mechanics and reduced lung inflammation and airspace enlargement and increased oxidative stress levels induced by elastase. BbCI may have therapeutic potential in chronic obstructive pulmonary disease.

Highlights

Chronic obstructive pulmonary disease (COPD) is a major cause of chronic respiratory morbidity and mortality and is the fifth leading cause of death worldwide [1]
The animals that received elastase and were treated with Bauhinia bauhinioides cruzipain inhibitor (BbCI) had a significant reduction in Ers compared to the ELA group (p < 0.05)
We found an increase in neutrophils, macrophages, and TNFα-positive cells in the ELA group compared to controls (p < 0.05)

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is a major cause of chronic respiratory morbidity and mortality and is the fifth leading cause of death worldwide [1]. A proteinaseantiproteinase imbalance is the most widely accepted hypothesis to explain lung tissue destruction In this context, elastase secreted by neutrophils and macrophages may play an important role in lung tissue destruction [2, 3]. To better understand the pathogenesis of emphysema, the elastase-induced model was developed 50 years ago. It is a simple and widely used method. In lung tissue we measured airspace enlargement, quantified neutrophils, TNFα-, MMP-9-, MMP-12-, TIMP-1-, iNOS-, and eNOS-positive cells, 8-iso-PGF2α, collagen, and elastic fibers in alveolar septa and airways. BbCI reduced elastase-induced changes in pulmonary mechanics, airspace enlargement and elastase-induced increases in total cells, and neutrophils in BALF. BbCI improved lung mechanics and reduced lung inflammation and airspace enlargement and increased oxidative stress levels induced by elastase. BbCI may have therapeutic potential in chronic obstructive pulmonary disease

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