Article Text

Download PDFPDF
Prosurvival activity for airway neutrophils in severe asthma
  1. Mohib Uddin1,
  2. Guangmin Nong1,
  3. Jonathan Ward1,
  4. Grégory Seumois1,
  5. Lynne R Prince2,
  6. Susan J Wilson1,
  7. Victoria Cornelius1,
  8. Gordon Dent1,
  9. Ratko Djukanović1
  1. 1Southampton NIHR Respiratory Biomedical Research Unit, Southampton Wellcome Trust Clinical Research Facility, Division of Infection, Inflammation and Immunity, University of Southampton School of Medicine, Southampton General Hospital, Southampton, UK
  2. 2Academic Unit of Respiratory Medicine, School of Medicine & Biomedical Sciences, University of Sheffield, Royal Hallamshire Hospital, Sheffield, UK
  1. Correspondence to Professor Ratko Djukanović, Southampton NIHR Respiratory Biomedical Research Unit, Division of Infection, Inflammation and Immunity, School of Medicine, University of Southampton School of Medicine, Mailpoint 810, Level F, Sir Henry Wellcome Laboratories, South Block, Southampton General Hospital, Southampton SO16 6YD, UK; r.djukanovic{at}southampton.ac.uk

Abstract

Background Airway neutrophilia is a recognised feature of chronic severe asthma, but the mechanisms that underlie this phenomenon are unknown. Evidence for factors present in airway secretions that prolong neutrophil survival has been sought and it has been hypothesised that these might be augmented in neutrophilic asthma.

Methods Non-smoking subjects with severe asthma (SA) or mild asthma (MA) and healthy control subjects (HC) underwent sputum induction. The SA group was subdivided into subjects with neutrophil counts above (SA-high) and those within the normal range (SA-low). Apoptotic neutrophils were enumerated in the cellular phase while the fluid phase was assessed for its ability to prolong the in vitro survival of blood-derived neutrophils using morphometric and flow cytometric analyses.

Results There was a significant difference between all four subject groups with respect to the percentage of apoptotic sputum neutrophils (Kruskal–Wallis, p=0.042). Cuzick test showed a highly significant (p=0.008) trend towards decreasing numbers of apoptotic neutrophils across the four groups with increasing asthma severity and neutrophil count. The sputum antiapoptotic activity was also different between the groups (p=0.039), with a highly significant (p=0.005) decreasing trend across the four groups. The survival effect could not be inhibited by blocking selective chemotaxin receptors, neutralising neutrophil survival factors, inhibiting phosphatidylinositol-3-kinase (using LY294002) or with pertussis toxin pretreatment. Similarly, it could not be explained by lipopolysaccharide contamination or by the presence of inhaled corticosteroids in sputum.

Conclusions These data demonstrate the capacity of as yet unidentified factor(s) in the airways of subjects with asthma to delay human neutrophil apoptosis and extend their lifespan as a potential mechanism contributing to unresolving airways neutrophilia in severe asthma.

  • Apoptosis
  • induced sputum
  • neutrophils
  • severe asthma
  • asthma
  • neutrophil biology

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Footnotes

  • Linked articles 134270.

  • MU and GN contributed equally to this work.

  • Funding This research was funded by the Division of Infection, Inflammation and Immunity, University of Southampton School of Medicine.

  • Competing interests None.

  • Ethics approval The study was approved by the South and West Local Research Ethics Committee, Southampton, UK.

  • Provenance and peer review Not commissioned; externally peer reviewed.

Linked Articles