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

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.

Bauhinia Protease Inhibitors Attenuate Gastric Ulcer by Blocking Neutrophil Enzymes

“…Protease inhibitors have been purified from Bauhinia seeds, chemically characterized and classified in the plant-Kunitz family. The activities of these inhibitors on blood coagulation and fibrinolysis enzymes have been described as well as on enzymes involved in digestion and in inflammation [5][6][7]. It is noteworthy that despite their similar structural characteristics, these inhibitors differ in inhibitory specificity on the XIIa and Xa coagulation factors.…”

Proteases and Their Inhibitors in Chronic Obstructive Pulmonary Disease

“…Bauhinia bauhinioides L. , a plant from the Caesalpinioideae sub-family has been shown to secrete many protease inhibitors. Among them, Bauhinia bauhinioides Kallikrein proteinase Inhibitor [ 73 ] (rBbKI) and Bauhinia bauhinioide scruzipain inhibitor [ 74 ] (BbCI) have been found to effectively ameliorate elastase-induced emphysema ( Figure 1 ). In a model of elastase-induced emphysema model, rBbKI was shown to effectively reduce elastase-induced inflammation and extracellular matrix remodeling.…”

O efeito do inibidor de proteinase de origem vegetal CrataBL, sobre a inflamação pulmonar alérgica crônica em camundongos Balb/c

“…Os resultados obtidos com outros modelos animais de inflamação, prétratados com os inibidores de proteinases BbCI e BbKI, sugeriram uma potencial ação anti-inflamatória desses inibidores (Oliveira et al, 2010;Almeida-Reis et al, 2012).…”

“…Este fato se deve, possivelmente, pela capacidade da CrataBL neutralizar o efeito da heparina (Ferreira et al, 2013), pois sabe-se que a mesma bloqueia a ativação de proteases e, assim, a destruição das fibras elásticas localizadas nas estruturas estudadas. Uma resposta similar foi observada em estudos que utilizaram um inibidor direto da atividade proteolítica desta enzima, o BbCI (Almeida-Reis et al, 2012;Marques et al, 2012).…”