Zheng Zeguang, Qi Yafei, Xu Xiaoming, Jiang Hua, Li Zhengtu, Yang Quan, Zhang Chenting, Zhang Kedong, Chen Rongchang, Wang Jian, Lu Wenju
State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou 510120, China.
Central Hospital of Panyu District, Guangzhou 511470, China.
J Thorac Dis. 2017 Jul;9(7):1873-1882. doi: 10.21037/jtd.2017.06.63.
Mucin 1 (MUC1) is a membrane tethered protein on airway epithelial cells. This protein is upregulated and plays an important anti-inflammatory role during acute lung inflammation. However, the relationship between sputum MUC1 level and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is unknown.
The levels of MUC1, IL-8, and TNF-α in induced sputum from 78 COPD patients were assessed by ELISA. The association between COPD exacerbation and MUC1 fragment levels was analyzed. An acute airway inflammation mouse model was established by intranasal LPS inhalation. The expression of Muc1 in lung and the levels of Muc1, TNF-α and KC in BAL fluid from mice were determined with western blotting and ELISA, respectively.
Higher levels of MUC1 membrane-tethered (CT) and extracellular (EC) fragments, cytokines TNF-α and IL-8, more leucocyte and neutrophil counts were found in sputum from COPD patients in acute than in remission phase. Linear regression analysis confirmed that the level of sputum MUC1 CT fragment is positively correlated with sputum neutrophil number and patients' age; whereas the sputum EC fragment level is correlated inversely with FEV1/FVC value and positively with patients' age. Inhalation of lipopolysaccharide (LPS) induced acute lung inflammation in mice which exhibited increased levels of Muc1 CT fragment in lung and only Muc1 EC fragment increase in BAL fluid.
Unlike pure bacterial induced lung inflammation, both sputum MUC1 CT and EC fragments are increased during acute exacerbation of COPD. The clinical benefits from measuring the changes of various sputum MUC1 fragments in AECOPD need to be elucidated in future studies.
黏蛋白1（MUC1）是气道上皮细胞上的一种膜锚定蛋白。该蛋白在急性肺部炎症期间上调并发挥重要的抗炎作用。然而，痰液MUC1水平与慢性阻塞性肺疾病急性加重（AECOPD）之间的关系尚不清楚。
采用酶联免疫吸附测定法（ELISA）评估78例慢性阻塞性肺疾病（COPD）患者诱导痰中MUC1、白细胞介素-8（IL-8）和肿瘤坏死因子-α（TNF-α）的水平。分析COPD急性加重与MUC1片段水平之间的关联。通过鼻内吸入脂多糖（LPS）建立急性气道炎症小鼠模型。分别用蛋白质免疫印迹法和ELISA法测定小鼠肺组织中Muc1的表达以及支气管肺泡灌洗液（BALF）中Muc1、TNF-α和KC的水平。
与缓解期相比，COPD患者急性发作期痰液中MUC1膜锚定（CT）片段和细胞外（EC）片段、细胞因子TNF-α和IL-8水平更高，白细胞和中性粒细胞计数更多。线性回归分析证实，痰液MUC1 CT片段水平与痰液中性粒细胞数量和患者年龄呈正相关；而痰液EC片段水平与第1秒用力呼气容积/用力肺活量（FEV1/FVC）值呈负相关，与患者年龄呈正相关。吸入脂多糖（LPS）可诱导小鼠发生急性肺部炎症，表现为肺组织中Muc1 CT片段水平升高，而BALF中仅Muc1 EC片段增加。
与单纯细菌诱导的肺部炎症不同，COPD急性加重期痰液中MUC1的CT和EC片段均增加。未来研究需要阐明检测AECOPD中各种痰液MUC1片段变化的临床益处。
