University of Cambridge, Cambridge, United Kingdom.
Am J Respir Cell Mol Biol. 2013 May;48(5):531-9. doi: 10.1165/rcmb.2012-0492TR.
Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide and has few effective therapies. It is characterized by anomalous and persistent inflammation, both local and systemic. Neutrophilic inflammation predominates in the COPD airway wall and lumen, but, despite the presence of abundant innate immune cells, the progressive clinical course of the disease is punctuated by recurrent infection-driven exacerbations. An extensive body of evidence (from cell culture to murine models and finally to the susceptibility of human patients with α1-antitrypsin deficiency to develop COPD) implicates neutrophil elastase and other neutrophil-derived proteases as key mediators of the tissue damage and relentless decline in lung function that occurs in this condition. In addition to the well recognized role of cytokines in modulating neutrophil function and survival, it has recently become apparent that hypoxia can influence neutrophil function, with impaired killing of pathogenic bacteria, enhanced release of proteases, and delayed apoptosis. This destructive neutrophil phenotype is predicted to be highly detrimental in the setting of the COPD microenvironment.
慢性阻塞性肺疾病（COPD）是全球第四大致死原因，目前治疗方法有限。它的特征是局部和全身异常且持续的炎症。中性粒细胞炎症在 COPD 气道壁和管腔中占主导地位，但是，尽管存在大量先天免疫细胞，疾病的进行性临床过程仍会被反复感染引起的恶化所打断。大量证据（从细胞培养到小鼠模型，最后是α1-抗胰蛋白酶缺乏症患者易患 COPD）表明中性粒细胞弹性蛋白酶和其他中性粒细胞衍生的蛋白酶是导致组织损伤和肺功能持续下降的关键介质。除了细胞因子在调节中性粒细胞功能和存活方面的作用外，最近还发现缺氧可以影响中性粒细胞的功能，导致对病原菌的杀伤能力受损、蛋白酶释放增强以及细胞凋亡延迟。这种破坏中性粒细胞的表型在 COPD 微环境中极有可能造成严重损害。
