Gao J, Ohlmeier S, Nieminen P, Toljamo T, Tiitinen S, Kanerva T, Bingle L, Araujo B, Rönty M, Höyhtyä M, Bingle C D, Mazur W, Pulkkinen V
HUCH Heart and Lung Center, Department of Pulmonary Medicine, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland;
Proteomics Core Facility, Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland;
Am J Physiol Lung Cell Mol Physiol. 2015 Jul 1;309(1):L17-26. doi: 10.1152/ajplung.00082.2015. Epub 2015 May 15.
A previous study involving a proteomic screen of induced sputum from smokers and patients with chronic obstructive pulmonary disease (COPD) demonstrated elevated levels of bactericidal/permeability-increasing fold-containing protein B1 (BPIFB1). The aim of the present study was to further evaluate the association of sputum BPIFB1 levels with smoking and longitudinal changes in lung function in smokers with COPD. Sputum BPIFB1 was characterized by two-dimensional gel electrophoresis and mass spectrometry. The expression of BPIFB1 in COPD was investigated by immunoblotting and immunohistochemistry using sputum and lung tissue samples. BPIFB1 levels were also assessed in induced sputum from nonsmokers (n = 31), smokers (n = 169), and patients with COPD (n = 52) via an ELISA-based method. The longitudinal changes in lung function during the 4-year follow-up period were compared with the baseline sputum BPIFB1 levels. In lung tissue samples, BPIFB1 was localized to regions of goblet cell metaplasia. Secreted and glycosylated BPIFB1 was significantly elevated in the sputum of patients with COPD compared with that of smokers and nonsmokers. Sputum BPIFB1 levels correlated with pack-years and lung function as measured by forced expiratory volume in 1 s (FEV1) % predicted and FEV1/FVC (forced vital capacity) at baseline and after the 4-year follow-up in all participants. The changes in lung function over 4 years were significantly associated with BPIFB1 levels in current smokers with COPD. In conclusion, higher sputum concentrations of BPIFB1 were associated with changes of lung function over time, especially in current smokers with COPD. BPIFB1 may be involved in the pathogenesis of smoking-related lung diseases.
一项先前的研究对吸烟者和慢性阻塞性肺疾病（COPD）患者的诱导痰进行了蛋白质组学筛查，结果显示杀菌/通透性增加蛋白B1（BPIFB1）水平升高。本研究的目的是进一步评估痰中BPIFB1水平与吸烟以及COPD吸烟者肺功能纵向变化之间的关联。通过二维凝胶电泳和质谱对痰中的BPIFB1进行表征。使用痰液和肺组织样本，通过免疫印迹和免疫组织化学研究COPD中BPIFB1的表达。还通过基于酶联免疫吸附测定（ELISA）的方法对非吸烟者（n = 31）、吸烟者（n = 169）和COPD患者（n = 52）的诱导痰中的BPIFB1水平进行了评估。将4年随访期内肺功能的纵向变化与基线痰BPIFB1水平进行比较。在肺组织样本中，BPIFB1定位于杯状细胞化生区域。与吸烟者和非吸烟者相比，COPD患者痰液中分泌型和糖基化的BPIFB1显著升高。在所有参与者中，基线时以及4年随访后，痰BPIFB1水平与吸烟包年数以及通过1秒用力呼气量（FEV1）占预计值百分比和FEV1/用力肺活量（FVC）测量的肺功能相关。4年内肺功能的变化与COPD现吸烟者的BPIFB1水平显著相关。总之，痰中较高浓度的BPIFB1与肺功能随时间的变化相关，尤其是在COPD现吸烟者中。BPIFB1可能参与吸烟相关肺部疾病的发病机制。
