Prosurvival activity for airway neutrophils in severe asthma

Uddin, Mohib; Nong, Guangmin; Ward, Jonathan; Seumois, Grégory; Prince, Lynne R.; Wilson, Susan J.; Cornelius, Victoria; Dent, Gordon; Djukanović, Ratko

doi:10.1136/thx.2009.120741

Cited by 117 publications

(119 citation statements)

References 52 publications

(39 reference statements)

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“…Extended neutrophil lifespan through decreased apoptosis is observed in patients with asthma 11 with acute coronary syndrome 12 and results in increased disease severity. Lifespan extension through prosurvival signals produced under inflammatory conditions may also increase the capacity of neutrophils to undergo phenotypic and functional changes and account for neutrophil heterogeneity.…”

Section: An Adaptable Lifespanmentioning

confidence: 99%

Neutrophil heterogeneity: implications for homeostasis and pathogenesis

Silvestre-Roig

Hidalgo

Soehnlein

2016

Blood

359

305

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Neutrophils are polymorphonuclear leukocytes of the phagocytic system that act as first line of host defense against invading pathogens but are also important mediators of inflammation-induced injury. In contrast to other members of the innate immune system, neutrophils are classically considered a homogenous population of terminally differentiated cells with a well-defined and highly conserved function. Indeed, their short lifespan, the absent proliferative capacity, their limited ability to produce large amounts of cytokines, and the failure to recirculate from the tissue to the bloodstream have sustained this idea. However, increasing evidence over the last decade has demonstrated an unexpected phenotypic heterogeneity and functional versatility of the neutrophil population. Far beyond their antimicrobial functions, neutrophils are emerging as decision-shapers during innate and adaptive immune responses. These emerging discoveries open a new door to understand the role of neutrophils during homeostatic but also pathogenic immune processes. Thus, this review details novel insights of neutrophil phenotypic and functional heterogeneity during homeostasis and disease.

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Section: An Adaptable Lifespanmentioning

confidence: 99%

Neutrophil heterogeneity: implications for homeostasis and pathogenesis

Silvestre-Roig

Hidalgo

Soehnlein

2016

Blood

359

305

View full text Add to dashboard Cite

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“…There is also evidence for an increase in factors promoting airway neutrophil viability in severe asthma (40). Furthermore, the role of Th17 lymphocytes in asthmatic airway inflammation is being investigated (41).…”

Section: Noneosinophilic Asthmamentioning

confidence: 99%

Untangling asthma phenotypes and endotypes

Agache

Akdiş

Jutel

et al. 2012

Allergy

286

235

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Asthma phenotypes have been developed to address the complexities of the disease. However, owing to a lack of longitudinal studies, little is known about the onset as well as the stability of phenotypes. Distinguishing phenotypes with regard to the severity or duration of the disease is essential. A phenotype covers the clinically relevant properties of the disease, but does not show the direct relationship to disease etiology and pathophysiology. Different pathogenetic mechanisms might cause similar asthma symptoms and might be operant in a certain phenotype. These putative mechanisms are addressed by the term 'endotype'. Classification of asthma based on endotypes provides advantages for epidemiological, genetic, and drug-related studies. A successful definition of endotypes should link key pathogenic mechanisms with the asthma phenotype. Thus, the identification of corresponding molecular biomarkers for individual pathogenic mechanism underlying phenotypes or subgroups within a phenotype is important. Whether newly defined asthma endotypes predict the individual course of asthma has to be validated in longitudinal studies. The accurate endotyping reflects natural history of asthma and should help to predict treatment response. Thus, understanding asthma endotypes might be useful in clinical practice.

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“…Yet, there are no known data that compellingly support a role of this pharmacological treatment in patients; quite the opposite: in a careful biopsy study, GIZYCKI et al [4] could not find any effect of corticosteroid treatment on neutrophil apoptosis compared with placebo treatment in chronic obstructive pulmonary disease. Furthermore, UDDIN et al [5] excluded a role of corticosteroid treatment as a factor in pro-survival activity for airway neutrophils in severe asthma. Lack of support for apoptosis-related effects actually lends weight to the findings of ZIJLSTRA et al [1], suggesting that a chemoattractant such as CCL20 could be involved in corticosteroid-induced airway neutrophilia.…”

Section: Glucocorticoids Induce the Production Of The Chemoattractantmentioning

confidence: 99%

“…Work from different laboratories demonstrates reduced lumen neutrophils along with bronchial wall neutrophilia in corticosteroid-treated patients (reviewed in [8]). In these cases, corticosteroid-induced neutrophil attractants [5,6] may have retained neutrophils in the bronchial wall, preventing their elimination by the transepithelial exit route [8].…”

Section: Glucocorticoids Induce the Production Of The Chemoattractantmentioning

confidence: 99%