Nontypeable Haemophilus influenzae induces sustained lung oxidative stress and protease expression

Paul Thomas King, Roleen Sharma, Kim O'Sullivan, Stavros Selemidis, Steven Lim, Naghmeh Radhakrishna, Camden Yeung-Wah Lo, Jyotika Prasad, Judith Mary Callaghan, Peter McLaughlin, Michael Farmer, Daniel P Steinfort, Barton Ruthven Jennings, James Ngui, Bradley Randal Scott Broughton, Belinda Thomas, Ama-Tawiah Essilfie, Michael John Hickey, Peter Holmes, Philip M Hansbro & 2 others Philip G Bardin, Stephen Roger Holdsworth

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)1 - 17
Number of pages17
JournalPLoS ONE
Volume10
Issue number3 (Art. No.: e0120371)
DOIs
Publication statusPublished - 2015

Cite this

King, Paul Thomas ; Sharma, Roleen ; O'Sullivan, Kim ; Selemidis, Stavros ; Lim, Steven ; Radhakrishna, Naghmeh ; Lo, Camden Yeung-Wah ; Prasad, Jyotika ; Callaghan, Judith Mary ; McLaughlin, Peter ; Farmer, Michael ; Steinfort, Daniel P ; Jennings, Barton Ruthven ; Ngui, James ; Broughton, Bradley Randal Scott ; Thomas, Belinda ; Essilfie, Ama-Tawiah ; Hickey, Michael John ; Holmes, Peter ; Hansbro, Philip M ; Bardin, Philip G ; Holdsworth, Stephen Roger. / Nontypeable Haemophilus influenzae induces sustained lung oxidative stress and protease expression. In: PLoS ONE. 2015 ; Vol. 10, No. 3 (Art. No.: e0120371). pp. 1 - 17.
@article{1a9fedc74f674af1b99aa1d44494afb5,
title = "Nontypeable Haemophilus influenzae induces sustained lung oxidative stress and protease expression",
abstract = "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.",
author = "King, {Paul Thomas} and Roleen Sharma and Kim O'Sullivan and Stavros Selemidis and Steven Lim and Naghmeh Radhakrishna and Lo, {Camden Yeung-Wah} and Jyotika Prasad and Callaghan, {Judith Mary} and Peter McLaughlin and Michael Farmer and Steinfort, {Daniel P} and Jennings, {Barton Ruthven} and James Ngui and Broughton, {Bradley Randal Scott} and Belinda Thomas and Ama-Tawiah Essilfie and Hickey, {Michael John} and Peter Holmes and Hansbro, {Philip M} and Bardin, {Philip G} and Holdsworth, {Stephen Roger}",
year = "2015",
doi = "10.1371/journal.pone.0120371",
language = "English",
volume = "10",
pages = "1 -- 17",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "3 (Art. No.: e0120371)",

}

King, PT, Sharma, R, O'Sullivan, K, Selemidis, S, Lim, S, Radhakrishna, N, Lo, CY-W, Prasad, J, Callaghan, JM, McLaughlin, P, Farmer, M, Steinfort, DP, Jennings, BR, Ngui, J, Broughton, BRS, Thomas, B, Essilfie, A-T, Hickey, MJ, Holmes, P, Hansbro, PM, Bardin, PG & Holdsworth, SR 2015, 'Nontypeable Haemophilus influenzae induces sustained lung oxidative stress and protease expression' PLoS ONE, vol. 10, no. 3 (Art. No.: e0120371), pp. 1 - 17. https://doi.org/10.1371/journal.pone.0120371

Nontypeable Haemophilus influenzae induces sustained lung oxidative stress and protease expression. / King, Paul Thomas; Sharma, Roleen; O'Sullivan, Kim; Selemidis, Stavros; Lim, Steven; Radhakrishna, Naghmeh; Lo, Camden Yeung-Wah; Prasad, Jyotika; Callaghan, Judith Mary; McLaughlin, Peter; Farmer, Michael; Steinfort, Daniel P; Jennings, Barton Ruthven; Ngui, James; Broughton, Bradley Randal Scott; Thomas, Belinda; Essilfie, Ama-Tawiah; Hickey, Michael John; Holmes, Peter; Hansbro, Philip M; Bardin, Philip G; Holdsworth, Stephen Roger.

In: PLoS ONE, Vol. 10, No. 3 (Art. No.: e0120371), 2015, p. 1 - 17.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Nontypeable Haemophilus influenzae induces sustained lung oxidative stress and protease expression

AU - King, Paul Thomas

AU - Sharma, Roleen

AU - O'Sullivan, Kim

AU - Selemidis, Stavros

AU - Lim, Steven

AU - Radhakrishna, Naghmeh

AU - Lo, Camden Yeung-Wah

AU - Prasad, Jyotika

AU - Callaghan, Judith Mary

AU - McLaughlin, Peter

AU - Farmer, Michael

AU - Steinfort, Daniel P

AU - Jennings, Barton Ruthven

AU - Ngui, James

AU - Broughton, Bradley Randal Scott

AU - Thomas, Belinda

AU - Essilfie, Ama-Tawiah

AU - Hickey, Michael John

AU - Holmes, Peter

AU - Hansbro, Philip M

AU - Bardin, Philip G

AU - Holdsworth, Stephen Roger

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368769/pdf/pone.0120371.pdf

U2 - 10.1371/journal.pone.0120371

DO - 10.1371/journal.pone.0120371

M3 - Article

VL - 10

SP - 1

EP - 17

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 3 (Art. No.: e0120371)

ER -