De Smet Elise G, Seys Leen Jm, Verhamme Fien M, Vanaudenaerde Bart M, Brusselle Guy G, Bingle Colin D, Bracke Ken R
Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium.
Int J Chron Obstruct Pulmon Dis. 2017 Dec 19;13:11-27. doi: 10.2147/COPD.S144136. eCollection 2018.
Chronic obstructive pulmonary disease (COPD) is characterized by an abnormal inflammatory response in the lungs caused by the inhalation of noxious particles and gases. The airway epithelium has a protective function against these harmful agents by maintaining a physical barrier and by secreting defensive proteins, such as bactericidal/permeability-increasing fold-containing (BPIF) proteins, BPIFA1 and BPIFB1. However, inconsistent data regarding BPIFA1 expression in smokers and COPD patients have been reported to date. Therefore, we investigated the expression of BPIFA1 and BPIFB1 in a large cohort of never-smokers and smokers with and without COPD, both on the messenger RNA (mRNA) level in lung tissue and on the protein level in airway epithelium. Furthermore, we examined the correlation between BPIFA1 and BPIFB1 levels, goblet cell hyperplasia, and lung function measurements. and mRNA expressions were significantly increased in stage III-IV COPD patients compared with stage II COPD patients and subjects without COPD. In addition, protein levels in COPD patients were significantly increased in comparison with subjects without COPD. BPIFA1 and BPIFB1 levels were inversely correlated with measurements of airflow limitation and positively correlated with goblet cell hyperplasia. In addition, by the use of immunofluorescence double staining, we demonstrated the expression of BPIFB1 in goblet cells. In conclusion, we show that BPIFA1 and BPIFB1 levels are elevated in COPD patients and correlate with disease severity.
慢性阻塞性肺疾病（COPD）的特征是因吸入有害颗粒和气体而导致肺部出现异常炎症反应。气道上皮通过维持物理屏障以及分泌防御蛋白（如含杀菌/通透性增加折叠结构的蛋白（BPIF）、BPIFA1和BPIFB1）来对这些有害物质发挥保护作用。然而，迄今为止，关于吸烟者和COPD患者中BPIFA1表达的数据并不一致。因此，我们在一大群从不吸烟者以及患有和未患有COPD的吸烟者中，研究了肺组织中信使核糖核酸（mRNA）水平以及气道上皮中蛋白质水平的BPIFA1和BPIFB1表达。此外，我们还检测了BPIFA1和BPIFB1水平、杯状细胞增生与肺功能测量值之间的相关性。与II期COPD患者和无COPD的受试者相比，III-IV期COPD患者的 和 mRNA表达显著增加。此外，与无COPD的受试者相比，COPD患者的蛋白质水平显著升高。BPIFA1和BPIFB1水平与气流受限测量值呈负相关，与杯状细胞增生呈正相关。此外，通过免疫荧光双重染色，我们证实了BPIFB1在杯状细胞中的表达。总之，我们发现COPD患者中BPIFA1和BPIFB1水平升高，且与疾病严重程度相关。
