Department of Medicine, SUNY Downstate Medical Center, New York, New York, United States of America.
Department of Neurology, Columbia University, New York, New York, United States of America.
PLoS One. 2020 Feb 6;15(2):e0228279. doi: 10.1371/journal.pone.0228279. eCollection 2020.
Smoke exposure is known to decrease total pulmonary surfactant and alter its composition, but the role of surfactant in chronic obstructive pulmonary disease (COPD) remains unknown. We aimed to analyze the compositional changes in the surfactant lipidome in COPD and identify specific lipids associated with pulmonary function decline. Bronchoalveolar lavage (BAL) fluid was obtained from 12 former smokers with COPD and 5 non-smoking, non-asthmatic healthy control volunteers. Lipids were extracted and analyzed by liquid chromatography and mass spectrometry. Pulmonary function data were obtained by spirometry, and correlations of lung function with lipid species were determined. Wild-type C57BL/6 mice were exposed to 6 months of second-hand smoke in a full-body chamber. Surfactant lipids were decreased by 60% in subjects with COPD. All phospholipid classes were dramatically decreased, including ether phospholipids, which have not been studied in pulmonary surfactant. Availability of phospholipid, cholesterol, and sphingomyelin in BAL strongly correlated with pulmonary function and this was attributable to specific lipid species of phosphatidylcholine with surface tension reducing properties, and of phosphatidylglycerol with antimicrobial roles, as well as to other less studied lipid species. Mice exposed to smoke for six months recapitulated surfactant lipidomic changes observed in human subjects with COPD. In summary, we show that the surfactant lipidome is substantially altered in subjects with COPD, and decreased availability of phospholipids correlated with decreased pulmonary function. Further investigation of surfactant alterations in COPD would improve our understanding of its physiopathology and reveal new potential therapeutic targets.
烟雾暴露已知会降低肺表面活性剂总量并改变其成分，但表面活性剂在慢性阻塞性肺疾病（COPD）中的作用仍不清楚。我们旨在分析 COPD 中表面活性剂脂质组的组成变化，并确定与肺功能下降相关的特定脂质。从 12 名有 COPD 的前吸烟者和 5 名不吸烟、非哮喘的健康对照志愿者中获得支气管肺泡灌洗液（BAL）。通过液相色谱和质谱法提取和分析脂质。通过肺活量计获得肺功能数据，并确定肺功能与脂质种类的相关性。野生型 C57BL/6 小鼠在全身室中暴露于 6 个月的二手烟。COPD 患者的表面活性剂脂质减少了 60%。所有磷脂类都显著减少，包括醚磷脂，以前在肺表面活性剂中没有研究过。BAL 中磷脂、胆固醇和神经鞘磷脂的可用性与肺功能强烈相关，这归因于具有表面张力降低特性的磷脂酰胆碱的特定脂质种类，以及具有抗菌作用的磷脂酰甘油，以及其他研究较少的脂质种类。暴露于烟雾 6 个月的小鼠重现了在 COPD 患者中观察到的表面活性剂脂质组学变化。总之，我们表明，COPD 患者的表面活性剂脂质组发生了实质性改变，并且磷脂的可用性降低与肺功能下降相关。进一步研究 COPD 中的表面活性剂变化将提高我们对其病理生理学的理解，并揭示新的潜在治疗靶点。
