Horio Yuko, Ichiyasu Hidenori, Kojima Keisuke, Saita Naoki, Migiyama Yohei, Iriki Toyohisa, Fujii Kazuhiko, Niki Toshiro, Hirashima Mitsuomi, Kohrogi Hirotsugu
Department of Respiratory Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Department of Immunology and Immunopathology, Kagawa University, Kagawa, Japan.
PLoS One. 2017 Jul 12;12(7):e0180742. doi: 10.1371/journal.pone.0180742. eCollection 2017.
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.
慢性阻塞性肺疾病（COPD）的特征是不可逆的气流阻塞和肺气肿。肺部和气道的持续炎症及重塑导致肺功能下降和生活质量降低。半乳糖凝集素（Gal）-9作为免疫调节剂在多种疾病中发挥关键作用。然而，其在肺气肿发病机制中的作用尚不清楚。本研究调查Gal-9是否参与猪胰弹性蛋白酶（PPE）诱导的肺气肿模型中的肺部炎症和肺气肿变化。
从PPE滴注前1天至第5天，每天给小鼠皮下注射一次Gal-9。在肺气肿发展过程中，收集肺组织和支气管肺泡灌洗液（BALF）。分析组织学和细胞学结果、BALF中趋化因子和基质金属蛋白酶（MMPs）的浓度，以及Gal-9治疗对中性粒细胞的影响。
Gal-9抑制了PPE诱导的肺气肿的病理变化。Gal-9治疗的肺气肿小鼠的平均线性截距（Lm）显著低于PBS治疗的肺气肿小鼠（分别为66.1±3.3μm和118.8±14.8μm；p<0.01）。Gal-9减少了BALF中中性粒细胞的数量以及MMP-9、MMP-2和金属蛋白酶组织抑制剂（TIMP）-1的水平。BALF中中性粒细胞的数量与MMPs水平显著相关。有趣的是，体外Gal-9预处理抑制了中性粒细胞的趋化活性和中性粒细胞产生MMP-9。此外，在Gal-9缺陷小鼠中，与野生型（WT）小鼠相比，PPE诱导的肺气肿进展显著（分别为108.7±6.58μm和77.19±6.97μm；p<0.01）。
这些结果表明，Gal-9通过抑制中性粒细胞浸润和降低MMPs水平来保护PPE诱导的炎症和肺气肿。外源性Gal-9可能是COPD的一种潜在治疗药物。
