NHMRC Centre for Respiratory and Sleep Medicine, Faculty of Health, School of Medicine and Public Health, The University of Newcastle, Callaghan, NSW 2308, Australia.
Mediators Inflamm. 2013;2013:462934. doi: 10.1155/2013/462934. Epub 2013 Mar 31.
Chronic obstructive pulmonary disease (COPD) is a common and serious respiratory disease, particularly in older individuals, characterised by fixed airway obstruction and persistent airway neutrophilia. The mechanisms that lead to these features are not well established. We investigated the contribution of age, prior smoking, and fixed airflow obstruction on sputum neutrophils, TLR2 expression, and markers of neutrophilic inflammation. Induced sputum from adults with COPD (n = 69) and healthy controls (n = 51) was examined. A sputum portion was dispersed, total, differential cell count and viability recorded, and supernatant assayed for CXCL8, matrix metalloproteinase- (MMP-) 9, neutrophil elastase, and soluble TLR2. Peripheral blood cells (n = 7) were stimulated and TLR2 activation examined. TLR2 levels were increased with ageing, while sputum neutrophils and total sputum MMP-9 levels increased with age, previous smoking, and COPD. In multivariate regression, TLR2 gene expression and MMP-9 levels were significant independent contributors to the proportion of sputum neutrophils after adjustment for age, prior smoking, and the presence of airflow obstruction. TLR2 stimulation led to enhanced release of MMP-9 from peripheral blood granulocytes. TLR2 stimulation activates neutrophils for MMP-9 release. Efforts to understand the mechanisms of TLR2 signalling and subsequent MMP-9 production in COPD may assist in understanding neutrophilic inflammation in COPD.
慢性阻塞性肺疾病（COPD）是一种常见且严重的呼吸系统疾病，尤其在老年人中较为常见，其特征为固定气道阻塞和持续气道中性粒细胞增多。导致这些特征的机制尚未完全明确。我们研究了年龄、既往吸烟和固定气流阻塞对痰中性粒细胞、TLR2 表达和中性粒细胞炎症标志物的影响。我们检查了 COPD 患者（n = 69）和健康对照者（n = 51）的诱导痰。分散一部分痰液，记录总细胞计数、分类细胞计数和细胞活力，并检测上清液中的 CXCL8、基质金属蛋白酶-（MMP-）9、中性粒细胞弹性蛋白酶和可溶性 TLR2。刺激外周血细胞（n = 7）并检查 TLR2 激活情况。TLR2 水平随年龄增长而增加，而痰中性粒细胞和总痰 MMP-9 水平随年龄、既往吸烟和 COPD 而增加。在多变量回归中，TLR2 基因表达和 MMP-9 水平是调整年龄、既往吸烟和气流阻塞存在后痰中性粒细胞比例的独立重要贡献因素。TLR2 刺激导致外周血粒细胞中 MMP-9 的释放增加。TLR2 刺激激活中性粒细胞释放 MMP-9。努力了解 COPD 中 TLR2 信号和随后 MMP-9 产生的机制可能有助于理解 COPD 中的中性粒细胞炎症。
