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主要特征。肺与气道的持续性炎症及重塑可引发肺功能减退与生活质量下降。半乳糖凝集素-9（Galectin-9，Gal-9）作为免疫调节剂在多种疾病中发挥关键调控作用，但其在肺气肿发病机制中的作用尚未明确。本研究旨在探讨Gal-9是否参与猪胰弹性蛋白酶（Porcine Pancreatic Elastase, PPE）诱导的肺气肿模型的肺部炎症反应及肺气肿病变进程。
材料与方法：于经气管滴注PPE前1天至第5天，每日1次给小鼠皮下注射Gal-9。在肺气肿病变进展过程中，采集小鼠肺组织与支气管肺泡灌洗液（Bronchoalveolar Lavage Fluid, BALF）。对组织学与细胞学检测结果、BALF中趋化因子及基质金属蛋白酶（Matrix Metalloproteinases, MMPs）浓度，以及Gal-9干预对中性粒细胞的影响进行分析。
研究结果：Gal-9可抑制PPE诱导的肺气肿病理改变。Gal-9处理组肺气肿小鼠的平均线性截距（Mean Linear Intercept, Lm）显著低于PBS处理组肺气肿小鼠（分别为66.1±3.3 μm与118.8±14.8 μm；p<0.01）。Gal-9可降低BALF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）与基质金属蛋白酶组织抑制剂-1（Tissue Inhibitor of Metalloproteinases, TIMP)-1的水平。BALF中中性粒细胞数量与MMPs水平呈显著正相关。值得注意的是，体外Gal-9预处理可抑制中性粒细胞的趋化活性及中性粒细胞分泌MMP-9。此外，与野生型（Wild Type, WT）小鼠相比，Gal-9基因敲除小鼠的PPE诱导肺气肿病变进展更为显著（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，Gal-9可通过抑制中性粒细胞浸润及降低MMPs水平，减轻PPE诱导的炎症反应与肺气肿。外源性Gal-9有望成为COPD的潜在治疗药物。