Nontypeable haemophilus influenzae induces sustained lung oxidative stress and protease expression

King, PT; Sharma, R; O'Sullivan, K; Selemidis, S; Lim, S; Radhakrishna, N; Lo, C; Prasad, J; Callaghan, J; McLaughlin, P; Farmer, M; Steinfort, D; Jennings, B; Ngui, J; Broughton, BRS; Thomas, B; Essilfie, AT; Hickey, M; Holmes, PW; Hansbro, P; Bardin, PG; Holdsworth, SR

Nontypeable haemophilus influenzae induces sustained lung oxidative stress and protease expression

King, PT Sharma, R O'Sullivan, K Selemidis, S Lim, S Radhakrishna, N Lo, C Prasad, J Callaghan, J McLaughlin, P Farmer, M Steinfort, D Jennings, B Ngui, J Broughton, BRS Thomas, B Essilfie, AT Hickey, M Holmes, PW Hansbro, P

Bardin, PG Holdsworth, SR

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Publication Type:: Journal Article
Citation:: PLoS ONE, 2015, 10 (3)
Issue Date:: 2015-03-20

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Field	Value	Language
dc.contributor.author	King, PT	en_US
dc.contributor.author	Sharma, R	en_US
dc.contributor.author	O'Sullivan, K	en_US
dc.contributor.author	Selemidis, S	en_US
dc.contributor.author	Lim, S	en_US
dc.contributor.author	Radhakrishna, N	en_US
dc.contributor.author	Lo, C	en_US
dc.contributor.author	Prasad, J	en_US
dc.contributor.author	Callaghan, J	en_US
dc.contributor.author	McLaughlin, P	en_US
dc.contributor.author	Farmer, M	en_US
dc.contributor.author	Steinfort, D	en_US
dc.contributor.author	Jennings, B	en_US
dc.contributor.author	Ngui, J	en_US
dc.contributor.author	Broughton, BRS	en_US
dc.contributor.author	Thomas, B	en_US
dc.contributor.author	Essilfie, AT	en_US
dc.contributor.author	Hickey, M	en_US
dc.contributor.author	Holmes, PW	en_US
dc.contributor.author	Hansbro, P https://orcid.org/0000-0002-4741-3035	en_US
dc.contributor.author	Bardin, PG	en_US
dc.contributor.author	Holdsworth, SR	en_US
dc.date.available	2015-01-21	en_US
dc.date.issued	2015-03-20	en_US
dc.identifier.citation	PLoS ONE, 2015, 10 (3)	en_US
dc.identifier.uri	http://hdl.handle.net/10453/128820
dc.description.abstract	© 2015 King et al. Nontypeable Haemophilus influenzae (NTHi) is a prevalent bacterium found in a variety of chronic respiratory diseases. The role of this bacterium in the pathogenesis of lung inflammation is not well defined. In this study we examined the effect of NTHi on two important lung inflammatory processes 1), oxidative stress and 2), protease expression. Bronchoalveolar macrophages were obtained from 121 human subjects, blood neutrophils from 15 subjects, and human-lung fibroblast and epithelial cell lines from 16 subjects. Cells were stimulated with NTHi to measure the effect on reactive oxygen species (ROS) production and extracellular trap formation. We also measured the production of the oxidant, 3-nitrotyrosine (3-NT) in the lungs of mice infected with this bacterium. NTHi induced widespread production of 3-NT in mouse lungs. This bacterium induced significantly increased ROS production in human fibroblasts, epithelial cells, macrophages and neutrophils; with the highest levels in the phagocytic cells. In human macrophages NTHi caused a sustained, extracellular production of ROS that increased over time. The production of ROS was associated with the formation of macrophage extracellular trap-like structures which co-expressed the protease metalloproteinase-12. The formation of the macrophage extracellular trap-like structures was markedly inhibited by the addition of DNase. In this study we have demonstrated that NTHi induces lung oxidative stress with macrophage extracellular trap formation and associated protease expression. DNase inhibited the formation of extracellular traps.	en_US
dc.relation.ispartof	PLoS ONE	en_US
dc.relation.isbasedon	10.1371/journal.pone.0120371	en_US
dc.subject.classification	General Science & Technology	en_US
dc.subject.mesh	Lung	en_US
dc.subject.mesh	Extracellular Space	en_US
dc.subject.mesh	Macrophages	en_US
dc.subject.mesh	Phagocytes	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Inbred BALB C	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Haemophilus influenzae	en_US
dc.subject.mesh	Reactive Oxygen Species	en_US
dc.subject.mesh	Deoxyribonucleases	en_US
dc.subject.mesh	Endopeptidases	en_US
dc.subject.mesh	Bacterial Typing Techniques	en_US
dc.subject.mesh	Bronchoalveolar Lavage	en_US
dc.subject.mesh	Cell Polarity	en_US
dc.subject.mesh	Oxidative Stress	en_US
dc.subject.mesh	Middle Aged	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Extracellular Traps	en_US
dc.title	Nontypeable haemophilus influenzae induces sustained lung oxidative stress and protease expression	en_US
dc.type	Journal Article
utslib.citation.volume	3	en_US
utslib.citation.volume	10	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access
pubs.issue	3	en_US
pubs.publication-status	Published	en_US
pubs.volume	10	en_US

Abstract:

© 2015 King et al. Nontypeable Haemophilus influenzae (NTHi) is a prevalent bacterium found in a variety of chronic respiratory diseases. The role of this bacterium in the pathogenesis of lung inflammation is not well defined. In this study we examined the effect of NTHi on two important lung inflammatory processes 1), oxidative stress and 2), protease expression. Bronchoalveolar macrophages were obtained from 121 human subjects, blood neutrophils from 15 subjects, and human-lung fibroblast and epithelial cell lines from 16 subjects. Cells were stimulated with NTHi to measure the effect on reactive oxygen species (ROS) production and extracellular trap formation. We also measured the production of the oxidant, 3-nitrotyrosine (3-NT) in the lungs of mice infected with this bacterium. NTHi induced widespread production of 3-NT in mouse lungs. This bacterium induced significantly increased ROS production in human fibroblasts, epithelial cells, macrophages and neutrophils; with the highest levels in the phagocytic cells. In human macrophages NTHi caused a sustained, extracellular production of ROS that increased over time. The production of ROS was associated with the formation of macrophage extracellular trap-like structures which co-expressed the protease metalloproteinase-12. The formation of the macrophage extracellular trap-like structures was markedly inhibited by the addition of DNase. In this study we have demonstrated that NTHi induces lung oxidative stress with macrophage extracellular trap formation and associated protease expression. DNase inhibited the formation of extracellular traps.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/128820