Priority Research Centre for Asthma and Respiratory Diseases, The University of Newcastle, Callaghan, New South Wales, Australia.
PLoS One. 2011 Mar 31;6(3):e18426. doi: 10.1371/journal.pone.0018426.
Chronic obstructive pulmonary disease (COPD) is characterised by irreversible airflow obstruction, neutrophilic airway inflammation and chronic bacterial colonisation, however the role of the innate immune response in the pathogenesis of COPD remains unclear.
Induced sputum was obtained from adults with COPD (n=22), and healthy controls (n=29) and was processed for differential cell counts. The sputum supernatant was assayed for innate immune mediators using ELISA, whilst sputum gene expression was measured using real-time PCR. Peripheral blood neutrophils were isolated and their response to lipopolysaccaride (LPS) stimulation was assessed in a subgroup of participants with COPD (n=13) and healthy controls (n=21).
Participants with COPD had significantly higher protein levels of interleukin (IL)-8, and neutrophil elastase (NE) and detection of oncostatin M (OSM) compared to healthy controls. Gene expression for toll-like receptor (TLR) 2, IL-8 and OSM were also significantly higher in COPD participants. The level of IL-1β, surfactant protein (SP)-A, matrix metalloproteinase (MMP)-9 and TLR4 mRNA was not significantly different between groups. The level of innate immune response markers were highly associated with the presence of sputum neutrophils, each other and the degree of airflow limitation (FEV1/FVC). Peripheral blood neutrophils from participants with COPD had an increased response to stimulation by LPS; with a greater fold increase in the production of IL-8 and MMP-9 protein, and gene expression of IL-8, TLR2 and TLR4.
The innate immune response is increased in the airways and circulating neutrophils in COPD, and may be an important mechanism involved in disease pathogenesis.
慢性阻塞性肺疾病（COPD）的特征是气流不可逆阻塞、中性粒细胞气道炎症和慢性细菌定植，但先天免疫反应在 COPD 发病机制中的作用仍不清楚。
从 COPD 患者（n=22）和健康对照者（n=29）中获取诱导痰，并进行差异细胞计数。通过 ELISA 检测痰液上清液中的先天免疫介质，通过实时 PCR 测量痰液基因表达。在 COPD 患者亚组（n=13）和健康对照组（n=21）中分离外周血中性粒细胞，并评估其对脂多糖（LPS）刺激的反应。
与健康对照组相比，COPD 患者的白细胞介素（IL）-8 和中性粒细胞弹性蛋白酶（NE）蛋白水平以及抑瘤素 M（OSM）检测显著升高。COPD 患者的 TLR2、IL-8 和 OSM 基因表达也显著升高。IL-1β、表面活性剂蛋白（SP）-A、基质金属蛋白酶（MMP）-9 和 TLR4mRNA 的水平在两组之间无显著差异。先天免疫反应标志物的水平与痰液中性粒细胞的存在、彼此之间以及气流受限程度（FEV1/FVC）高度相关。COPD 患者的外周血中性粒细胞对 LPS 刺激的反应增强；IL-8 和 MMP-9 蛋白的产生以及 IL-8、TLR2 和 TLR4 的基因表达的倍数增加更大。
COPD 患者的气道和循环中性粒细胞中的先天免疫反应增加，可能是疾病发病机制中的一个重要机制。
