National Heart and Lung Institute, Imperial College London, London, UK.
Department of Infectious Disease, Imperial College London, London, UK.
Immunology. 2021 Dec;164(4):701-721. doi: 10.1111/imm.13419. Epub 2021 Oct 4.
Neutrophils are critical components of the body's immune response to infection, being loaded with a potent arsenal of toxic mediators and displaying immense destructive capacity. Given the potential of neutrophils to impart extensive tissue damage, it is perhaps not surprising that when augmented these cells are also implicated in the pathology of inflammatory diseases. Prominent neutrophilic inflammation is a hallmark feature of patients with chronic lung diseases such as chronic obstructive pulmonary disease, severe asthma, bronchiectasis and cystic fibrosis, with their numbers frequently associating with worse prognosis. Accordingly, it is anticipated that neutrophils are central to the pathology of these diseases and represent an attractive therapeutic target. However, in many instances, evidence directly linking neutrophils to the pathology of disease has remained somewhat circumstantial and strategies that have looked to reduce neutrophilic inflammation in the clinic have proved largely disappointing. We have classically viewed neutrophils as somewhat crude, terminally differentiated, insular and homogeneous protagonists of pathology. However, it is now clear that this does not do the neutrophil justice, and we now recognize that these cells exhibit heterogeneity, a pronounced awareness of the localized environment and a remarkable capacity to interact with and modulate the behaviour of a multitude of cells, even exhibiting anti-inflammatory, pro-resolving and pro-repair functions. In this review, we discuss evidence for the role of neutrophils in chronic lung disease and how our evolving view of these cells may impact upon our perceived assessment of their contribution to disease pathology and efforts to target them therapeutically.
中性粒细胞是机体对感染的免疫反应的关键组成部分，它们携带着强大的毒性介质库，并具有巨大的破坏能力。鉴于中性粒细胞有可能造成广泛的组织损伤，当这些细胞被增强时，它们也可能与炎症性疾病的病理学有关，这也许并不奇怪。在慢性肺部疾病患者中，如慢性阻塞性肺疾病、严重哮喘、支气管扩张和囊性纤维化，中性粒细胞炎症明显，是其特征性表现，其数量常常与预后较差相关。因此，可以预期中性粒细胞是这些疾病病理学的核心，并且代表了一个有吸引力的治疗靶点。然而，在许多情况下，将中性粒细胞与疾病病理学直接联系起来的证据仍然有些间接，并且在临床上试图减少中性粒细胞炎症的策略已被证明在很大程度上令人失望。我们通常将中性粒细胞视为病理学中较为原始、终末分化、孤立和同质的主角。然而，现在很明显，这种观点并不公正，我们现在认识到这些细胞表现出异质性，对局部环境有明显的认识，并且具有与多种细胞相互作用和调节其行为的显著能力，甚至表现出抗炎、促解决和促修复功能。在这篇综述中，我们讨论了中性粒细胞在慢性肺部疾病中的作用的证据，以及我们对这些细胞的不断发展的认识可能如何影响我们对其对疾病病理学的贡献的看法，以及对其进行治疗的努力。
