Our evolving view of neutrophils in defining the pathology of chronic lung disease

Abstract

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.

Mobilisation of HLA‐F on the surface of bronchial epithelial cells and platelets in asthmatic patients

“…These chronic lung diseases and their severe clinical complications constitute a serious public health burden with high morbidity and mortality rates worldwide. 1 Asthma, which affects 358 million people around the globe and causes 495,000 deaths each year, is characterised by the recruitment, survival and activation of inflammatory cells occurring within the airways, and is associated with structural airway abnormalities. 2,3 Human bronchial epithelium cells (HBEC) play a main role in immune cells response.…”

“…These diseases are subsequently exacerbated due to acute or chronic infections, accelerated lung function impairment and respiratory insufficiency. These chronic lung diseases and their severe clinical complications constitute a serious public health burden with high morbidity and mortality rates worldwide 1 …”

Asthma Therapies on Pulmonary Tuberculosis Pneumonia in Predominant Bronchiectasis–Asthma Combination

“…The elevated neutrophil levels in sputum were associated with more exacerbations, low lung function, and greater duration and severity of bronchiectasis. Similarly, neutrophil elastase, derived from neutrophils, was found to be associated with an increased severity of bronchiectasis ( Polverino et al, 2018 ; Mincham et al, 2021 ). The subgroups of the BCAS cohort such as BCAOS (7) include the asthma + bronchiectasis + COPD, and this triple component has complicated asthma, COPD, and bronchiectasis with high activity of the neutrophil ( Polverino et al, 2018 ; Coman et al, 2018 ; Mihălț;an and Constantin, 2019 ; Mincham et al, 2021 ).…”

“…Similarly, neutrophil elastase, derived from neutrophils, was found to be associated with an increased severity of bronchiectasis ( Polverino et al, 2018 ; Mincham et al, 2021 ). The subgroups of the BCAS cohort such as BCAOS (7) include the asthma + bronchiectasis + COPD, and this triple component has complicated asthma, COPD, and bronchiectasis with high activity of the neutrophil ( Polverino et al, 2018 ; Coman et al, 2018 ; Mihălț;an and Constantin, 2019 ; Mincham et al, 2021 ). The excessive activation of neutrophils results in the release of neutrophil elastase, leading to microenvironments that predispose to PTB or pneumonia among the BCAS cohort ( Porto and Stein, 2016 ; Domon et al, 2018 ; Mihălț;an and Constantin, 2019 ).…”

A persistent neutrophil-associated immune signature characterises post-COVID19 pulmonary sequelae

“…Mechanistically, neutrophils may therefore drive brogenesis through release of proteases (e.g. neutrophil elastase and matrix metalloproteins (MMPs)) that can degrade extracellular matrix (ECM) proteins such as types I-IV collagens 44 . Neutrophil elastase and selected MMPs (e.g.…”