Xie Liang, Li Qingmin, Dong Ran, Zhao Kaishun, Feng Yun, Bao Zhiyao, Zhou Min
Department of Pulmonary and Critical Care Medicine, Shanghai Institute of Respiratory Disease, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Department of Cardiology, Henan Provincial Peoples Hospital, Zhengzhou, China.
Int J Chron Obstruct Pulmon Dis. 2018 Apr 13;13:1145-1155. doi: 10.2147/COPD.S153326. eCollection 2018.
Inflammation is an important cause of COPD. Alveolar macrophages are the major innate immune cells that have an important role in COPD pathology. Class A scavenger receptor (SR-A) is a pattern recognition receptor expressed on macrophages. This study investigates the role of SR-A in COPD progression via regulation of inflammation.
SR-A expression in COPD patients and control subjects (smokers and nonsmokers without COPD) was measured by immunohistochemistry, immunofluorescence, and real-time PCR. The cytokine levels in BAL were measured by enzyme-linked immunosorbent assay. To further prove our hypothesis, we treated RAW264.7 cells that overexpress SR-A with lipopolysaccharides, poly(I:C), cigarette smoke extract, and H1N1 influenza separated from patients for 24 h and examined the levels of inflammatory cytokines.
In both groups, COPD and smokers without COPD, SR-A expression level was upregulated in alveolar macrophages. SR-A mRNA level was positively correlated with inflammatory cytokines and negatively correlated with FEV% predicted in COPD patients. In RAW-SR-A cells, level of inflammatory cytokines was significantly higher when compared with control ones.
SR-A could increase inflammation stimulated by cigarette smoke extracts, bacteria, and virus, leading to long-term inflammation in COPD, and thus might be used as a new therapeutic target for COPD treatment.
炎症是慢性阻塞性肺疾病（COPD）的一个重要病因。肺泡巨噬细胞是主要的固有免疫细胞，在COPD病理过程中起重要作用。A类清道夫受体（SR-A）是一种在巨噬细胞上表达的模式识别受体。本研究通过调节炎症来探讨SR-A在COPD进展中的作用。
采用免疫组织化学、免疫荧光和实时聚合酶链反应检测COPD患者以及对照受试者（吸烟者和无COPD的非吸烟者）中SR-A的表达。通过酶联免疫吸附测定法检测支气管肺泡灌洗液（BAL）中的细胞因子水平。为进一步验证我们的假设，我们用脂多糖、聚肌苷酸-聚胞苷酸、香烟烟雾提取物以及从患者分离出的H1N1流感病毒处理过表达SR-A的RAW264.7细胞24小时，并检测炎症细胞因子水平。
在COPD组和无COPD的吸烟者这两组中，肺泡巨噬细胞中SR-A的表达水平均上调。在COPD患者中，SR-A信使核糖核酸水平与炎症细胞因子呈正相关，与预测的第一秒用力呼气容积（FEV%）呈负相关。在RAW-SR-A细胞中，与对照细胞相比，炎症细胞因子水平显著更高。
SR-A可增加香烟烟雾提取物、细菌和病毒刺激引起的炎症，导致COPD中的长期炎症，因此可能用作COPD治疗的新靶点。
