Research Article: Protective effect of Galectin-9 in murine model of lung emphysema: Involvement of neutrophil migration and MMP-9 production

Date Published: July 12, 2017

Publisher: Public Library of Science

Author(s): Yuko Horio, Hidenori Ichiyasu, Keisuke Kojima, Naoki Saita, Yohei Migiyama, Toyohisa Iriki, Kazuhiko Fujii, Toshiro Niki, Mitsuomi Hirashima, Hirotsugu Kohrogi, Paul Proost.


Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and pulmonary emphysema. Persistent inflammation and remodeling of the lungs and airways result in reduced lung function and a lower quality of life. Galectin (Gal)-9 plays a crucial role as an immune modulator in various diseases. However, its role in the pathogenesis of pulmonary emphysema is unknown. This study investigates whether Gal-9 is involved in pulmonary inflammation and changes in emphysema in a porcine pancreatic elastase (PPE)-induced emphysema model.

Gal-9 was administered to mice subcutaneously once daily from 1 day before PPE instillation to day 5. During the development of emphysema, lung tissue and bronchoalveolar lavage fluid (BALF) were collected. Histological and cytological findings, concentrations of chemokines and matrix metalloproteinases (MMPs) in the BALF, and the influence of Gal-9 treatment on neutrophils were analyzed.

Gal-9 suppressed the pathological changes of PPE-induced emphysema. The mean linear intercept (Lm) of Gal-9-treated emphysema mice was significantly lower than that of PBS-treated emphysema mice (66.1 ± 3.3 μm vs. 118.8 ± 14.8 μm, respectively; p < 0.01). Gal-9 decreased the number of neutrophils and levels of MMP-9, MMP-2 and tissue inhibitor of metalloproteinases (TIMP)-1 in the BALF. The number of neutrophils in the BALF correlated significantly with MMPs levels. Interestingly, Gal-9 pretreatment in vitro inhibited the chemotactic activity of neutrophils and MMP-9 production from neutrophils. Furthermore, in Gal-9-deficient mice, PPE-induced emphysema progressed significantly compared with that in wild–type (WT) mice (108.7 ± 6.58 μm vs. 77.19 ± 6.97 μm, respectively; p < 0.01). These results suggest that Gal-9 protects PPE-induced inflammation and emphysema by inhibiting the infiltration of neutrophils and decreasing MMPs levels. Exogenous Gal-9 could be a potential therapeutic agent for COPD.

Partial Text

Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death in the world [1], and its prevalence and mortality rates are steadily increasing. Therefore, COPD is a serious health problem. Even though COPD occurs predominantly in smokers, the fact that only 15%–20% of smokers develop COPD suggests an interaction between genetic, environmental, and other factors in the etiology of COPD [2–4].

In this study, we addressed the contribution of Gal-9 to the pathogenesis of emphysema. We found that Gal-9 attenuated PPE-induced emphysema in a murine model by inhibiting the infiltration of neutrophils and MMP-9 production in the lung. Gal-9 treatment inhibited the neutrophil chemotaxis in response to chemoattractant. In Gal-9 deficient mice, PPE-induced pulmonary emphysema was exacerbated by the enhanced neutrophil recruitment in the lung.




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