Data from: Protective effect of Galectin-9 in murine model of lung emphysema: involvement of neutrophil migration and MMP-9 production

Purpose: 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.
Materials and Methods: 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.
Results: 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).
Conclusions: 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.

研究目的：慢性阻塞性肺疾病（Chronic Obstructive Pulmonary Disease, COPD）以不可逆性气流受限及肺气肿为特征。肺部与气道的持续性炎症及重塑会导致肺功能下降与生活质量降低。半乳糖凝集素（Galectin, Gal）-9在多种疾病中作为免疫调节剂发挥关键作用，但其在肺气肿发病机制中的作用尚不明确。本研究旨在探讨半乳糖凝集素-9是否参与猪胰弹性蛋白酶（porcine pancreatic elastase, PPE）诱导的肺气肿模型中的肺部炎症反应及肺气肿病变变化。
材料与方法：于猪胰弹性蛋白酶滴注前1天至第5天，每日1次皮下给予小鼠半乳糖凝集素-9。在肺气肿发生过程中，采集肺组织与支气管肺泡灌洗液（bronchoalveolar lavage fluid, BALF）。分析组织学与细胞学结果、支气管肺泡灌洗液中趋化因子及基质金属蛋白酶（matrix metalloproteinases, MMPs）的浓度，以及半乳糖凝集素-9治疗对中性粒细胞的影响。
结果：半乳糖凝集素-9可抑制猪胰弹性蛋白酶诱导的肺气肿病理改变。半乳糖凝集素-9治疗组肺气肿小鼠的平均肺间距（mean linear intercept, Lm）显著低于磷酸盐缓冲液（phosphate buffered saline, PBS）治疗组（分别为66.1±3.3 μm与118.8±14.8 μm；p<0.01）。半乳糖凝集素-9可降低支气管肺泡灌洗液中中性粒细胞数量，以及基质金属蛋白酶-9（MMP-9）、基质金属蛋白酶-2（MMP-2）和金属蛋白酶组织抑制剂（tissue inhibitor of metalloproteinases, TIMP）-1的水平。支气管肺泡灌洗液中中性粒细胞数量与基质金属蛋白酶水平呈显著相关。值得注意的是，体外半乳糖凝集素-9预处理可抑制中性粒细胞的趋化活性及其产生基质金属蛋白酶-9。此外，与野生型（wild-type, WT）小鼠相比，半乳糖凝集素-9基因缺陷小鼠的猪胰弹性蛋白酶诱导的肺气肿病变显著加重（分别为108.7±6.58 μm与77.19±6.97 μm；p<0.01）。
结论：上述结果表明，半乳糖凝集素-9可通过抑制中性粒细胞浸润并降低基质金属蛋白酶水平，从而减轻猪胰弹性蛋白酶诱导的炎症反应与肺气肿。外源性半乳糖凝集素-9有望成为慢性阻塞性肺疾病的潜在治疗药物。