Chronic Obstructive Pulmonary Disease-Specific Gene Expression Signatures of Alveolar Macrophages as well as Peripheral Blood Monocytes Overlap and Correlate with Lung Function
Chronic Obstructive Pulmonary Disease-Specific Gene Expression Signatures of Alveolar Macrophages as well as Peripheral Blood Monocytes Overlap and Correlate with Lung Function
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DOI：
10.1159/000324297
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发表时间：
2011-01-01
期刊：
影响因子：
3.7
通讯作者：
Nagy, Laszlo
中科院分区：
文献类型：
--
作者：
Poliska, Szilard;Csanky, Eszter;Nagy, Laszlo
背景：慢性阻塞性肺疾病（COPD）是一种慢性炎症性疾病，以进行性气流限制和显著的肺外（全身）影响为特征，可导致合并症，尽管COPD的发病机制在很大程度上尚不确定。来源于外周单核细胞（MO）的肺泡巨噬细胞（AM）似乎在启动和/或维持疾病进展中起关键作用。目的：鉴定疾病和细胞类型特异性基因表达谱和潜在的重叠，以诊断COPD，表征其进展并确定药物治疗的效果。方法：采用全基因表达分析进行初筛，获取COPD患者和健康对照的AMs和循环MOs的表达特征。采用实时定量聚合酶链反应对AMs（20例对照组，26例COPD患者）和MOs（16例对照组，22例COPD患者）的微阵列分析结果进行确认和验证。结果：我们已经确定了AMs和MOs中与COPD特异性相关的基因集。两种细胞类型之间存在重叠的基因。我们的数据还显示，AMs和MOs中copd特异性基因表达特征与预测FEV1的百分比相关。结论：在肺源性巨噬细胞和循环单核细胞中可以定义疾病特异性和重叠的基因表达特征。两种细胞类型中一些已证实的表达变化与肺功能相关，因此可以作为疾病进展的生物标志物。巴塞尔S. Karger股份有限公司版权所有
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 realtime 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. Copyright (C) 2011 S. Karger AG, Basel