背景:慢性阻塞性肺疾病(COPD)是发病率和死亡率的常见原因。在COPD中已经描述了失调和增强的免疫-炎症反应。最近的数据显示免疫反应受损,特别是,这些患者的干扰素(IFNs)信号通路。
目的:评价慢性阻塞性肺疾病(COPD)患者的外周肺,导致IFN产生的先天免疫反应的一些研究较少的关键成分的表达,包括:IFN受体(IFNAR1/IFNAR2),IRF-3和MDA-5。已经评估了与临床特征和炎症细胞谱的相关性。
方法:从58名接受胸外科手术的受试者中收集肺标本:22名COPD患者,21例肺功能正常的吸烟者(SC)和15例非吸烟者对照(nSC)。通过免疫组织化学定量外周血肺中嗜酸性粒细胞和活化NK细胞(NKp46)的IFNAR1,IFNAR2,IRF-3和MDA-5的表达。
结果:与nSC受试者相比,在COPD和SC中观察到IRF-3+肺泡巨噬细胞的显着增加。然而,在COPD患者中,IRF-3+肺泡巨噬细胞水平越低,FEV1越低,加重率越高.慢性支气管炎(CB)的存在也与低水平的IRF-3肺泡巨噬细胞有关。NKp46+细胞,但不是嗜酸性粒细胞,与nSC患者相比,COPD患者的发病率增加(p<0.0001)。
结论:吸烟与较高水平的先天性免疫反应相关,IRF-3+肺泡巨噬细胞和NKp46+细胞水平较高。在COPD中,恶化率,严重的气流阻塞和CB与较低水平的IRF-3表达相关,这表明先天免疫反应是该疾病特定临床特征的特征。
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a frequent cause of morbidity and mortality. Dysregulated and enhanced immune-inflammatory responses have been described in COPD. Recent data showed impaired immune responses and, in particular, of interferon (IFNs) signaling pathway in these patients.
OBJECTIVE: To evaluate in peripheral lung of COPD patients, the expression of some of the less investigated key components of the innate immune responses leading to IFN productions including: IFN-receptors (IFNAR1/IFNAR2), IRF-3 and MDA-5. Correlations with clinical traits and with the inflammatory cell profile have been assessed.
METHODS: Lung specimens were collected from 58 subjects undergoing thoracic surgery: 22 COPD patients, 21 smokers with normal lung function (SC) and 15 non-smoker controls (nSC). The expression of IFNAR1, IFNAR2, IRF-3 and MDA-5, of eosinophils and activated NK cells (NKp46+) were quantified in the peripheral lung by immunohistochemistry.
RESULTS: A significant increase of IRF-3 + alveolar macrophages were observed in COPD and SC compared with nSC subjects. However, in COPD patients, the lower the levels of IRF-3 + alveolar macrophages the lower the FEV1 and the higher the exacerbation rate. The presence of chronic bronchitis (CB) was also associated with low levels of IRF-3 + alveolar macrophages. NKp46 + cells, but not eosinophils, were increased in COPD patients compared to nSC patients (p < 0.0001).
CONCLUSIONS: Smoking is associated with higher levels of innate immune response as showed by higher levels of IRF-3 + alveolar macrophages and NKp46 + cells. In COPD, exacerbation rates, severe airflow obstruction and CB were associated with lower levels of IRF-3 expression, suggesting that innate immune responses characterize specific clinical traits of the disease.