Wan Arabella, Chen Dongshi
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Hastings Center for Pulmonary Research, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
J Respir Biol Transl Med. 2025 Mar;2(1). doi: 10.70322/jrbtm.2024.10022. Epub 2024 Dec 9.
Chronic obstructive pulmonary disease (COPD) and lung cancer are closely linked, with individuals suffering from COPD at a significantly higher risk of developing lung cancer. The mechanisms driving this increased risk are multifaceted, involving genomic instability, immune dysregulation, and alterations in the lung environment. Neutrophils, the most abundant myeloid cells in human blood, have emerged as critical regulators of inflammation in both COPD and lung cancer. Despite their short lifespan, neutrophils contribute to disease progression through various forms of programmed cell death, including apoptosis, necroptosis, ferroptosis, pyroptosis, and NETosis, a form of neutrophil death with neutrophil extracellular traps (NETs) formation. These distinct death pathways affect inflammatory responses, tissue remodeling, and disease progression in COPD and lung cancer. This review provides an in-depth exploration of the mechanisms regulating neutrophil death, the interplay between various cell death pathways, and their influence on disease progression. Additionally, we highlight emerging therapeutic approaches aimed at targeting neutrophil death pathways, presenting promising new interventions to enhance treatment outcomes in COPD and lung cancer.
慢性阻塞性肺疾病（COPD）与肺癌密切相关，患有COPD的个体患肺癌的风险显著更高。导致这种风险增加的机制是多方面的，涉及基因组不稳定、免疫失调和肺部环境改变。中性粒细胞是人类血液中最丰富的髓样细胞，已成为COPD和肺癌炎症的关键调节因子。尽管中性粒细胞寿命较短，但它们通过各种形式的程序性细胞死亡促进疾病进展，包括凋亡、坏死性凋亡、铁死亡、焦亡以及NETosis（一种伴有中性粒细胞胞外陷阱形成的中性粒细胞死亡形式）。这些不同的死亡途径影响COPD和肺癌中的炎症反应、组织重塑和疾病进展。本综述深入探讨了调节中性粒细胞死亡的机制、各种细胞死亡途径之间的相互作用及其对疾病进展的影响。此外，我们强调了针对中性粒细胞死亡途径的新兴治疗方法，提出了有前景的新干预措施以提高COPD和肺癌的治疗效果。
