Aberrant neutrophil functions in stable chronic obstructive pulmonary disease: The neutrophil as an immunotherapeutic target

Stockley, James; Walton, Georgia M; Lord, Janet M.; Sapey, Elizabeth

doi:10.1016/j.intimp.2013.05.035

Cited by 54 publications

(51 citation statements)

References 84 publications

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“…Neutrophil count and neutrophilic inflammatory mediators are higher within the airways, even in the stable (non-exacerbated) state in COPD [13]. Blood neutrophils also show an altered pattern of activity in the stable state in COPD, with impaired chemotaxis and reduced intracellular reactive oxygen species (ROS) production [14–16].…”

Section: Introductionmentioning

confidence: 99%

“…Evidence of further systemic immune dysregulation occurs during exacerbations with circulating neutrophils displaying up-regulation of inflammation-related genes, enhanced expression of cell adhesion molecules and elevated production of elastase and ROS [17–20]. Despite an abundance of data supporting the hypothesis that neutrophils are key effector cells in the development and progression of COPD [13], we could find no studies assessing blood neutrophil function of COPD patients according to exacerbation history.…”

Section: Introductionmentioning

confidence: 99%

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Impaired Blood Neutrophil Function in the Frequent Exacerbator of Chronic Obstructive Pulmonary Disease: A Proof-of-Concept Study

Jones

Robinson

Mohamed

et al. 2016

Lung

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PurposeThe underlying biological mechanisms of the frequent exacerbator phenotype of COPD remain unclear. We compared systemic neutrophil function in COPD patients with or without frequent exacerbations.MethodsWhole blood from COPD frequent exacerbators (defined as ≥2 moderate–severe exacerbations in the previous 2 years) and non-exacerbators (no exacerbations in the preceding 2 years) was assayed for neutrophil function. Neutrophil function in healthy ex-smoking volunteers was also measured as a control (reference) group.ResultsA total of 52 subjects were included in this study: 26 frequent exacerbators, 18 non-exacerbators and 8 healthy controls. COPD frequent exacerbators had blunted blood neutrophil fMLP-stimulated oxidative burst compared to both non-exacerbators (p < 0.01) and healthy controls (p < 0.001). There were no differences between COPD frequent exacerbators and non-exacerbators in blood neutrophil PMA-stimulated oxidative burst, but both COPD groups had reduced responses compared to healthy controls (p < 0.001). Bacterial-stimulated neutrophil degranulation was greater in frequent exacerbators than non-exacerbators (p < 0.05).ConclusionThis study is the first to report aberrant receptor-mediated blood neutrophil function in the frequent exacerbator of COPD.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impaired Blood Neutrophil Function in the Frequent Exacerbator of Chronic Obstructive Pulmonary Disease: A Proof-of-Concept Study

Jones

Robinson

Mohamed

et al. 2016

Lung

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show abstract

“…Neutrophilic airway inflammation is a major symptom of chronic obstructive pulmonary disease (COPD), a debilitating and progressive lung disease characterized by airway inflammation, airway remodeling, emphysema, expiratory airflow obstruction, and accelerated lung function decline (41). Smoking is the major risk factor for COPD, and the chronic and pathological lung inflammation that develops in COPD patients in response to smoking is predominantly characterized by neutrophilic infiltrates (45), which positively correlate with disease severity as measured by the degree of airflow obstruction, emphysema, and chronic bronchitis (48). The airway inflammation seen in COPD patients is mainly steroid insensitive since neither oral nor inhaled steroids are able to attenuate the numbers of inflammatory cells or reduce the expression levels of proinflammatory cytokines and chemokines in induced sputum and airway biopsies of COPD patients (1).…”

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confidence: 99%

Genetic variation associates with susceptibility for cigarette smoke-induced neutrophilia in mice

Pouwels

Heijink

Brouwer

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…It is also noteworthy that in COPD and non-CF bronchiectasis patients devoid of a hereditary CFTR defect, massive neutrophil transmigration also occurs in the lungs, with subsequent release of primary granules and impaired phagocytosis reminiscent of the picture seen in CF patients [95, 96]. This suggests that a primary defect in CFTR expression is not the root cause of neutrophilic inflammation in these disease contexts.…”

Section: Reviewmentioning

confidence: 99%

Neutrophil plasticity enables the development of pathological microenvironments: implications for cystic fibrosis airway disease

Margaroli

Tirouvanziam

2016

Mol Cell Pediatr

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IntroductionThe pathological course of several chronic inflammatory diseases, including cystic fibrosis, chronic obstructive pulmonary disease, and rheumatoid arthritis, features an aberrant innate immune response dominated by neutrophils. In cystic fibrosis, neutrophil burden and activity of neutrophil elastase in the extracellular fluid have been identified as strong predictors of lung disease severity.ReviewAlthough neutrophils are generally considered to be rigid, pre-programmed effector leukocytes, recent studies suggest extensive plasticity in how neutrophil functions unfold upon recruitment to peripheral tissues, and how they choose their ultimate fate. Indeed, upon migration to cystic fibrosis airways, neutrophils display dysregulated lifespan, metabolic activation, and altered effector and regulatory functions, consistent with profound adaptation and phenotypic reprogramming. Licensed by signals present in cystic fibrosis airway microenvironment to survive and develop these novel functions, neutrophils orchestrate, in partnership with the epithelium and with the resident microbiota, the evolution of a pathological microenvironment. This microenvironment is defined by altered proteolytic, redox, and metabolic balance and the presence of stable luminal structures in which neutrophils and microbes coexist.ConclusionsThe elucidation of molecular mechanisms driving neutrophil plasticity in vivo will open new treatment opportunities designed to modulate, rather than block, the crucial adaptive functions fulfilled by neutrophils. This review aims to outline emerging mechanisms of neutrophil plasticity and their participation in the building of pathological microenvironments in the context of cystic fibrosis and other diseases with similar features.

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Aberrant neutrophil functions in stable chronic obstructive pulmonary disease: The neutrophil as an immunotherapeutic target

Cited by 54 publications

References 84 publications

Impaired Blood Neutrophil Function in the Frequent Exacerbator of Chronic Obstructive Pulmonary Disease: A Proof-of-Concept Study

Impaired Blood Neutrophil Function in the Frequent Exacerbator of Chronic Obstructive Pulmonary Disease: A Proof-of-Concept Study

Genetic variation associates with susceptibility for cigarette smoke-induced neutrophilia in mice

Neutrophil plasticity enables the development of pathological microenvironments: implications for cystic fibrosis airway disease

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