School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Newcastle, NSW, Australia.
Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia.
Respirology. 2020 Jan;25(1):53-63. doi: 10.1111/resp.13722. Epub 2019 Oct 30.
COPD is a seriously disabling respiratory condition that inexorably progresses to disability and mortality. It affects approximately 10% of the population globally with a greater prevalence at advanced ages. Airway bacterial infections complicate the disease course in most COPD patients, leading to increased symptoms, more rapid decline in lung function, acute exacerbations and reduced quality of life. With increasing bacterial resistance to antibiotics and adverse effects of conventional treatments, new effective non-antibiotic antimicrobial therapies are urgently needed to manage COPD. Hypoxia-inducible factor (HIF)-1α is an important transcriptional regulator of cellular responses to hypoxia, oxidants and inflammation, and is overexpressed in the lungs of COPD patients. Recent evidence shows that increased HIF-1α expression can upregulate the platelet-activating factor receptor (PAFR) on the airway epithelial surface that is increased in smokers and particularly COPD patients. The receptor is utilized by PAFR-dependent bacteria (Streptococcus pneumoniae, Haemophilus influenzae and Pseudomonas aeruginosa) to induce infection in both the respiratory and gastrointestinal (GI) tracts. However, the importance and mechanism of HIF-1α in augmenting PAFR-dependent bacterial infections in COPD are poorly understood. Here, we review the evidence for the roles of local tissue hypoxia-induced inflammation, HIF-1α and PAFR in facilitating bacterial infections in COPD. Blocking PAFR may provide a novel antimicrobial approach to manage bacterial infections in COPD.
COPD 是一种严重致残的呼吸系统疾病，会不可避免地导致残疾和死亡。它影响着全球约 10%的人口，在老年人群中更为普遍。气道细菌感染使大多数 COPD 患者的疾病进程复杂化，导致症状加重、肺功能更快下降、急性加重和生活质量降低。随着抗生素耐药性的增加和传统治疗方法的不良反应，迫切需要新的有效非抗生素抗菌治疗方法来治疗 COPD。缺氧诱导因子（HIF）-1α 是细胞对缺氧、氧化剂和炎症反应的重要转录调节剂，在 COPD 患者的肺部过度表达。最近的证据表明，HIF-1α 表达的增加可以上调气道上皮表面的血小板激活因子受体（PAFR），在吸烟者中特别是 COPD 患者中增加。该受体被 PAFR 依赖性细菌（肺炎链球菌、流感嗜血杆菌和铜绿假单胞菌）利用，以诱导呼吸道和胃肠道（GI）的感染。然而，HIF-1α 在增强 COPD 中 PAFR 依赖性细菌感染中的作用及其机制尚不清楚。在这里，我们回顾了局部组织缺氧诱导的炎症、HIF-1α 和 PAFR 促进 COPD 中细菌感染的作用的证据。阻断 PAFR 可能为治疗 COPD 中的细菌感染提供一种新的抗菌方法。
