Neutrophil phenotypes in chronic lung disease

ABSTRACT

Introduction: Neutrophils are the most abundant inflammatory cells in the lungs of patients with chronic lung diseases, especially COPD, yet despite this, patients often experience repeated chest infections. Neutrophil function may be altered in disease, but the reasons are unclear. In chronic disease, sequential pro-inflammatory and pro-repair responses appear distorted. As understanding of neutrophil heterogeneity has expanded, it is suggested that different neutrophil phenotypes may impact on health and disease.

Areas covered: In this review, the definition of cellular phenotype, the implication of neutrophil surface markers and functions in chronic lung disease and the complex influences of external, local and genetic factors on these changes are discussed. Literature was accessed up to the 19 July 2019 using: PubMed, US National Library of Medicine National Institutes of Health and the National Centre for Biotechnology Information.

Expert opinion: As more is learned about neutrophils, the further we step from the classical view of neutrophils being unrefined killing machines to highly complex and finely tuned cells. Future therapeutics may aim to normalize neutrophil function, but to achieve this, knowledge of phenotypes in humans and how these relate to observed pathology and disease processes is required.

KEYWORDS:

• Neutrophils
• COPD
• Inflammation

Article highlights

• Neutrophils have been recognized for many years as not only being fundamental to host defense but also implicated in a wide array of chronic diseases, including lung disease.

• Neutrophils undergo important developmental changes in phenotype that enable their function as immune cells

• Changes occur to the neutrophil phenotype that enables a healthy response to infection and damage

• There are studies of altered neutrophil function in chronic lung disease, with the largest evidence base in chronic obstructive pulmonary disease. Here, reduced migratory accuracy, limited phagocytosis, increased degranulation and increased NETosis have been described, which is in keeping with the progressive tissue damage and recurrent infections experienced by many patients.

• aging has a key role to play in chronic lung disease, and the aging of neutrophils may have important implications for chronic lung disease

• Some studies suggest neutrophils may have distinct sub-populations or phenotypes. This includes the classical pro-inflammatory neutrophil, pro-angiogenic (repair) neutrophil and anti-inflammatory neutrophil. If these subgroups exist, it remains unclear how they have evolved.

• Understanding the mechanism of functional modification and the potential for health and harm with each modification might unlock new therapeutic processes which are sorely needed in chronic lung diseases.

Declaration of interest

MJ Hughes is a Wellcome Trust funded PhD Student. R Stockley is associated with NIHR and Alpha-1 Foundation and E Sapey is a member of Medical Research Council and NIHR. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

Manuscript was not funded.