Neutrophils and emerging targets for treatment in chronic obstructive pulmonary disease

Meijer, Mariska T.; Rijkers, Ger T.; Overveld, F. J. van

doi:10.1586/1744666x.2013.851347

Cited by 68 publications

(58 citation statements)

References 125 publications

(168 reference statements)

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“…The persistent presence of neutrophils in the lungs of COPD patients is thought to maintain inflammation through the release of active mediators such as proteolytic enzymes [5][6][7]. Paradoxically, neutrophils ).…”

Section: Discussionmentioning

confidence: 99%

“…On the contrary, high numbers of neutrophils recruited to the lungs positively correlate with poor prognosis [20]. Besides, the clinical course of COPD is punctuated by infection-driven acute exacerbations [5,6,21]. Thus, an understanding of the potential adverse effects of neutrophils on lung antimicrobial defence may provide insight for the development of new therapies to limit AE-COPD and attenuate the disease [22].…”

Section: Discussionmentioning

confidence: 99%

“…We and others previously demonstrated that IL-22 protects and regenerates respiratory epithelial cells upon infection with influenza virus and limits secondary bacterial infections [4]. COPD is also characterised by high numbers of leukocytes, such as neutrophils in the lungs [5,6]. The accumulation and activation of neutrophils in COPD result in the excessive secretion of inflammatory molecules.…”

Section: Introductionmentioning

confidence: 99%

“…The accumulation and activation of neutrophils in COPD result in the excessive secretion of inflammatory molecules. Many studies suggest that neutrophil-derived proteases such as elastase and cathepsin G are key mediators of lung damage [5][6][7]. Neutrophil proteases degrade soluble mediators or matrix components and alter cell surface receptors [5].…”

Section: Introductionmentioning

confidence: 99%

“…Defects in innate defence mechanisms have been documented in patients suffering from COPD, despite the abundance of innate immune cells such as neutrophils, which predominate in the airway wall and lumen of COPD patients [5,6]. Such immune defects may predispose COPD patients to viral or bacterial infections, which aggravate the disease.…”

Section: Introductionmentioning

confidence: 99%

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Neutrophil proteases alter the interleukin-22-receptor-dependent lung antimicrobial defence

et al. 2015

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Chronic obstructive pulmonary disease (COPD) is punctuated by episodes of infectiondriven acute exacerbations. Despite the life-threatening nature of these exacerbations, the underlying mechanisms remain unclear, although a high number of neutrophils in the lungs of COPD patients is known to correlate with poor prognosis. Interleukin (IL)-22 is a cytokine that plays a pivotal role in lung antimicrobial defence and tissue protection. We hypothesised that neutrophils secrete proteases that may have adverse effects in COPD, by altering the IL-22 receptor (IL-22R)-dependent signalling.Using in vitro and in vivo approaches as well as reverse transcriptase quantitative PCR, flow cytometry and/or Western blotting techniques, we first showed that pathogens such as the influenza virus promote IL-22R expression in human bronchial epithelial cells, whereas Pseudomonas aeruginosa, bacterial lipopolysaccharide or cigarette smoke do not. Most importantly, neutrophil proteases cleave IL-22R and impair IL-22-dependent immune signalling and expression of antimicrobial effectors such as β-defensin-2. This proteolysis resulted in the release of a soluble fragment of IL-22R, which was detectable both in cellular and animal models as well as in sputa from COPD patients with acute exacerbations.Hence, our study reveals an unsuspected regulation by the proteolytic action of neutrophil enzymes of IL-22-dependent lung host response. This process probably enhances pathogen replication, and ultimately COPD exacerbations. @ERSpublications Neutrophil proteases alter lung antimicrobial defence and may predispose to infection-triggered COPD exacerbations http://ow.ly/MHqEt

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Neutrophil proteases alter the interleukin-22-receptor-dependent lung antimicrobial defence

et al. 2015

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Nutrition in Inflammatory Lung Diseases

Aguilar-López

Olvera-Sandoval

Estrada-Luna

et al. 2019

Oxidative Stress in Lung Diseases

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Neutrophil-derived granule cargoes: paving the way for tumor growth and progression

Rawat

Syeda

Shrivastava

2021

Cancer Metastasis Rev

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Neutrophils are the key cells of our innate immune system mediating host defense via a range of effector functions including phagocytosis, degranulation, and NETosis. For this, they employ an arsenal of anti-microbial cargoes packed in their readily mobilizable granule subsets. Notably, the release of granule content is tightly regulated; however, under certain circumstances, their unregulated release can aggravate tissue damage and could be detrimental to the host. Several constituents of neutrophil granules have also been associated with various inflammatory diseases including cancer. In cancer setting, their excessive release may modulate tissue microenvironment which ultimately leads the way for tumor initiation, growth and metastasis. Neutrophils actively infiltrate within tumor tissues, wherein they show diverse phenotypic and functional heterogeneity. While most studies are focused at understanding the phenotypic heterogeneity of neutrophils, their functional heterogeneity, much of which is likely orchestrated by their granule cargoes, is beginning to emerge. Therefore, a better understanding of neutrophil granules and their cargoes will not only shed light on their diverse role in cancer but will also reveal them as novel therapeutic targets. This review provides an overview on existing knowledge of neutrophil granules and detailed insight into the pathological relevance of their cargoes in cancer. In addition, we also discuss the therapeutic approach for targeting neutrophils or their microenvironment in disease setting that will pave the way forward for future research.

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Neutrophils and emerging targets for treatment in chronic obstructive pulmonary disease

Cited by 68 publications

References 125 publications

Neutrophil proteases alter the interleukin-22-receptor-dependent lung antimicrobial defence

Neutrophil proteases alter the interleukin-22-receptor-dependent lung antimicrobial defence

Nutrition in Inflammatory Lung Diseases

Neutrophil-derived granule cargoes: paving the way for tumor growth and progression

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