Calero Carmen, Arellano Elena, Lopez-Villalobos Jose Luis, Sánchez-López Verónica, Moreno-Mata Nicolás, López-Campos José Luis
Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Hospital Virgen del Rocío, Sevilla, Spain.
BMC Pulm Med. 2014 May 30;14:95. doi: 10.1186/1471-2466-14-95.
Chronic systemic inflammatory syndrome has been implicated in the pathobiology of extrapulmonary manifestations of chronic obstructive pulmonary disease (COPD). We aimed to investigate which cell types within lung tissue are responsible for expressing major acute-phase reactants in COPD patients and disease-free ("resistant") smokers.
An observational case-control study was performed to investigate three different cell types in surgical lung samples of COPD patients and resistant smokers via expression of the C-reactive protein (CRP) and serum amyloid A (SAA1, SAA2 and SAA4) genes. Epithelial cells, macrophages and fibroblasts from the lung parenchyma were separated by magnetic microbeads (CD326, CD14 and anti-fibroblast), and gene expression was evaluated by RT-PCR.
The sample consisted of 74 subjects, including 40 COPD patients and 34 smokers without disease. All three cell types were capable of synthesizing these biomarkers to some extent. In fibroblasts, gene expression analysis of the studied biomarkers demonstrated increased SAA2 and decreased SAA1 in patients with COPD. In epithelial cells, there was a marked increase in CRP, which was not observed in fibroblasts or macrophages. In macrophages, however, gene expression of these markers was decreased in COPD patients compared to controls.
These results provide novel information regarding the gene expression of CRP and SAA in different cell types in the lung parenchyma. This study revealed differences in the expression of these markers according to cell type and disease status and contributes to the identification of cell types that are responsible for the secretion of these molecules.
慢性全身炎症综合征与慢性阻塞性肺疾病(COPD)的肺外表现的病理生物学有关。我们旨在研究肺组织中的哪些细胞类型负责在COPD患者和无疾病(“抗性”)吸烟者中表达主要急性期反应物。
进行了一项观察性病例对照研究,通过C反应蛋白(CRP)和血清淀粉样蛋白A(SAA1、SAA2和SAA4)基因的表达,研究COPD患者和抗性吸烟者手术肺样本中的三种不同细胞类型。通过磁性微珠(CD326、CD14和抗成纤维细胞)分离肺实质中的上皮细胞、巨噬细胞和成纤维细胞,并通过逆转录聚合酶链反应(RT-PCR)评估基因表达。
样本包括74名受试者,其中40名COPD患者和34名无疾病吸烟者。所有三种细胞类型都能够在一定程度上合成这些生物标志物。在成纤维细胞中,对所研究生物标志物的基因表达分析表明,COPD患者的SAA2增加而SAA1减少。在上皮细胞中,CRP有明显增加,而成纤维细胞或巨噬细胞中未观察到这种情况。然而,与对照组相比,COPD患者巨噬细胞中这些标志物的基因表达降低。
这些结果提供了关于肺实质中不同细胞类型中CRP和SAA基因表达的新信息。这项研究揭示了这些标志物根据细胞类型和疾病状态的表达差异,并有助于确定负责分泌这些分子的细胞类型。