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Prosurvival activity for airway neutrophils in severe asthma

Prosurvival activity for airway neutrophils in severe asthma
Prosurvival activity for airway neutrophils in severe asthma
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 (KruskaleWallis, p¼0.042). Cuzick test showed a highly significant (p¼0.008) 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 (p¼0.039), with a highly significant (p¼0.005) 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.
0040-6376
684-689
Uddin, Mohib
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Nong, Guangmin
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Ward, Jonathan
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Seumois, Gregory
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Prince, Lynne R.
e079bb3d-430b-4b65-9306-dc4f056da0f5
Wilson, Susan J.
21c6875d-6870-441b-ae7a-603562a646b8
Cornelius, Victoria
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Dent, Gordon
73559f2a-168a-4f3d-b478-f3838e77132f
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Uddin, Mohib
7b8953f2-baa0-4ad0-836b-ecb89cba70c2
Nong, Guangmin
7d3e91da-337b-4a6a-b8ab-9330eb9c854e
Ward, Jonathan
a8107b98-069d-4263-bd70-d29d79f07edc
Seumois, Gregory
0be7d3d6-5526-458c-aa5c-cce52410a2ed
Prince, Lynne R.
e079bb3d-430b-4b65-9306-dc4f056da0f5
Wilson, Susan J.
21c6875d-6870-441b-ae7a-603562a646b8
Cornelius, Victoria
b75c21d7-2c25-495c-9107-e39453a72bdd
Dent, Gordon
73559f2a-168a-4f3d-b478-f3838e77132f
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d

Uddin, Mohib, Nong, Guangmin, Ward, Jonathan, Seumois, Gregory, Prince, Lynne R., Wilson, Susan J., Cornelius, Victoria, Dent, Gordon and Djukanovic, Ratko (2010) Prosurvival activity for airway neutrophils in severe asthma. Thorax, 65 (8), 684-689. (doi:10.1136/thx.2009.120741).

Record type: Article

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 (KruskaleWallis, p¼0.042). Cuzick test showed a highly significant (p¼0.008) 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 (p¼0.039), with a highly significant (p¼0.005) 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.

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Published date: August 2010
Organisations: Community Clinical Sciences

Identifiers

Local EPrints ID: 161953
URI: http://eprints.soton.ac.uk/id/eprint/161953
ISSN: 0040-6376
PURE UUID: 0213a471-8793-441f-994f-31d261198b0f
ORCID for Jonathan Ward: ORCID iD orcid.org/0000-0002-9278-0002
ORCID for Susan J. Wilson: ORCID iD orcid.org/0000-0003-1305-8271
ORCID for Ratko Djukanovic: ORCID iD orcid.org/0000-0001-6039-5612

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Date deposited: 12 Aug 2010 11:13
Last modified: 22 Jan 2022 02:33

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Contributors

Author: Mohib Uddin
Author: Guangmin Nong
Author: Jonathan Ward ORCID iD
Author: Gregory Seumois
Author: Lynne R. Prince
Author: Susan J. Wilson ORCID iD
Author: Victoria Cornelius
Author: Gordon Dent

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