Jasper Alice E, McIver William J, Sapey Elizabeth, Walton Georgia M
Birmingham Acute Care Research, Institute of Inflammation and Ageing, University of Birmingham, UK, Birmingham, B15 2TT, UK.
F1000Res. 2019 Apr 26;8. doi: 10.12688/f1000research.18411.1. eCollection 2019.
Airway neutrophilia is a common feature of many chronic inflammatory lung diseases and is associated with disease progression, often regardless of the initiating cause. Neutrophils and their products are thought to be key mediators of the inflammatory changes in the airways of patients with chronic obstructive pulmonary disease (COPD) and have been shown to cause many of the pathological features associated with disease, including emphysema and mucus hypersecretion. Patients with COPD also have high rates of bacterial colonisation and recurrent infective exacerbations, suggesting that neutrophil host defence mechanisms are impaired, a concept supported by studies showing alterations to neutrophil migration, degranulation and reactive oxygen species production in cells isolated from patients with COPD. Although the role of neutrophils is best described in COPD, many of the pathological features of this disease are not unique to COPD and also feature in other chronic inflammatory airway diseases, including asthma, cystic fibrosis, alpha-1 anti-trypsin deficiency, and bronchiectasis. There is increasing evidence for immune cell dysfunction contributing to inflammation in many of these diseases, focusing interest on the neutrophil as a key driver of pulmonary inflammation and a potential therapeutic target than spans diseases. This review discusses the evidence for neutrophilic involvement in COPD and also considers their roles in alpha-1 anti-trypsin deficiency, bronchiectasis, asthma, and cystic fibrosis. We provide an in-depth assessment of the role of the neutrophil in each of these conditions, exploring recent advances in understanding, and finally discussing the possibility of common mechanisms across diseases.
气道中性粒细胞增多是许多慢性炎症性肺病的常见特征，并且与疾病进展相关，通常与起始病因无关。中性粒细胞及其产物被认为是慢性阻塞性肺疾病（COPD）患者气道炎症变化的关键介质，并且已被证明会导致许多与该疾病相关的病理特征，包括肺气肿和黏液高分泌。COPD患者还具有较高的细菌定植率和反复感染性加重，这表明中性粒细胞的宿主防御机制受损，这一概念得到了研究的支持，这些研究表明从COPD患者分离的细胞中中性粒细胞迁移、脱颗粒和活性氧生成发生了改变。虽然中性粒细胞的作用在COPD中描述得最为清楚，但该疾病的许多病理特征并非COPD所特有，在其他慢性炎症性气道疾病中也有表现，包括哮喘、囊性纤维化、α-1抗胰蛋白酶缺乏症和支气管扩张症。越来越多的证据表明免疫细胞功能障碍在许多这些疾病的炎症中起作用，这使得人们将兴趣集中在中性粒细胞上，认为它是肺部炎症的关键驱动因素以及一种潜在的跨疾病治疗靶点。本综述讨论了中性粒细胞参与COPD的证据，并考虑了它们在α-1抗胰蛋白酶缺乏症、支气管扩张症、哮喘和囊性纤维化中的作用。我们对中性粒细胞在每种疾病中的作用进行了深入评估，探讨了最新的认识进展，最后讨论了跨疾病共同机制的可能性。
