Supplementary Material for: Chronic Obstructive Pulmonary Disease-Specific Gene Expression Signatures of Alveolar Macrophages as well as Peripheral Blood Monocytes Overlap and Correlate with Lung Function

Background: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by progressive airflow limitation and significant extrapulmonary (systemic) effects that lead to co-morbid conditions, though the pathomechanism of COPD is largely undetermined. Alveolar macrophages (AM) derived from peripheral monocytes (MO) appear to play a key role in initiating and/or sustaining disease progression. Objectives: To identify disease- and cell type-specific gene expression profiles and potential overlaps in those in order to diagnose COPD, characterize its progression and determine the effect of drug treatment. Method: Global gene expression analysis was used for primary screening in order to obtain expression signatures of AMs and circulating MOs of COPD patients and healthy controls. The results of microarray analyses of AMs (20 controls and 26 COPD patients) and MOs (16 controls and 22 COPD patients) were confirmed and validated by real-time quantitative polymerase chain reaction. Results: We have identified gene sets specifically associated with COPD in AMs and MOs. There were overlapping genes between the two cell types. Our data also show that COPD-specific gene expression signatures in AMs and MOs correlate with percent of predicted FEV1. Conclusion: Disease-specific and overlapping gene expression signatures can be defined in lung-derived macrophages and also in circulating monocytes. Some of the validated expression changes in both cell types correlate with lung function and therefore could serve as biomarkers of disease progression.

背景：慢性阻塞性肺疾病（Chronic Obstructive Pulmonary Disease, COPD）是一种慢性炎症性疾病，以进行性气流受限和显著的肺外（全身）效应为特征，可引发多种合并症，但目前其发病机制在很大程度上尚未明确。源自外周血单核细胞（Monocytes, MO）的肺泡巨噬细胞（Alveolar Macrophages, AM）似乎在启动和/或维持疾病进展过程中发挥关键作用。
研究目标：旨在识别疾病特异性与细胞类型特异性基因表达谱，并探寻这些谱之间的潜在重叠，以实现COPD的临床诊断、疾病进展特征刻画以及药物治疗效果的评估。
研究方法：采用全局基因表达分析开展初步筛选，以获取COPD患者与健康对照者的肺泡巨噬细胞及循环单核细胞的表达特征。通过实时定量聚合酶链式反应（real-time quantitative polymerase chain reaction），对肺泡巨噬细胞（20名健康对照、26名COPD患者）及单核细胞（16名健康对照、22名COPD患者）的基因芯片分析结果进行了验证与确证。
研究结果：本研究已鉴定出肺泡巨噬细胞与单核细胞中与COPD特异性相关的基因集，且两种细胞类型间存在重叠基因。数据同时显示，肺泡巨噬细胞与单核细胞中的COPD特异性基因表达谱与预测一秒用力呼气容积占比（percent of predicted FEV1）呈显著相关性。
研究结论：可在肺源性巨噬细胞及循环单核细胞中确定疾病特异性及重叠性基因表达谱。两种细胞类型中部分经验证的表达变化与肺功能指标相关，因此可作为疾病进展的潜在生物标志物。