Accumulation mode particles and LPS exposure induce TLR-4 dependent and independent inflammatory responses in the lung
Abstract Background Accumulation mode particles (AMP) are formed from engine combustion and make up the inhalable vapour cloud of ambient particulate matter pollution. Their small size facilitates dispersal and subsequent exposure far from their original source, as well as the ability to penetrate a...
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doaj-a17b4426dfd347149aa757af7de0dc152020-11-24T22:21:42ZengBMCRespiratory Research1465-993X2018-01-0119111010.1186/s12931-017-0701-zAccumulation mode particles and LPS exposure induce TLR-4 dependent and independent inflammatory responses in the lungAngela M. Fonceca0Graeme R. Zosky1Elizabeth M. Bozanich2Erika N. Sutanto3Anthony Kicic4Paul S. McNamara5Darryl A. Knight6Peter D. Sly7Debra J. Turner8Stephen M. Stick9School of Paediatrics and Child Health, University of Western AustraliaTelethon Kids InstituteTelethon Kids InstituteTelethon Kids InstituteSchool of Paediatrics and Child Health, University of Western AustraliaDepartment of Women’s and Children’s Health, Institute of Translational Medicine, University of LiverpoolSchool of Biomedical Sciences and Pharmacy, University of NewcastleQueensland Children’s Medical Research Institute, University of QueenslandTelethon Kids InstituteSchool of Paediatrics and Child Health, University of Western AustraliaAbstract Background Accumulation mode particles (AMP) are formed from engine combustion and make up the inhalable vapour cloud of ambient particulate matter pollution. Their small size facilitates dispersal and subsequent exposure far from their original source, as well as the ability to penetrate alveolar spaces and capillary walls of the lung when inhaled. A significant immuno-stimulatory component of AMP is lipopolysaccharide (LPS), a product of Gram negative bacteria breakdown. As LPS is implicated in the onset and exacerbation of asthma, the presence or absence of LPS in ambient particulate matter (PM) may explain the onset of asthmatic exacerbations to PM exposure. This study aimed to delineate the effects of LPS and AMP on airway inflammation, and potential contribution to airways disease by measuring airway inflammatory responses induced via activation of the LPS cellular receptor, Toll-like receptor 4 (TLR-4). Methods The effects of nebulized AMP, LPS and AMP administered with LPS on lung function, cellular inflammatory infiltrate and cytokine responses were compared between wildtype mice and mice not expressing TLR-4. Results The presence of LPS administered with AMP appeared to drive elevated airway resistance and sensitivity via TLR-4. Augmented TLR4 driven eosinophilia and greater TNF-α responses observed in AMP-LPS treated mice independent of TLR-4 expression, suggests activation of allergic responses by TLR4 and non-TLR4 pathways larger than those induced by LPS administered alone. Treatment with AMP induced macrophage recruitment independent of TLR-4 expression. Conclusions These findings suggest AMP-LPS as a stronger stimulus for allergic inflammation in the airways then LPS alone.http://link.springer.com/article/10.1186/s12931-017-0701-zAsthmaTLR-4PMLPSAMPCOPD |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Angela M. Fonceca Graeme R. Zosky Elizabeth M. Bozanich Erika N. Sutanto Anthony Kicic Paul S. McNamara Darryl A. Knight Peter D. Sly Debra J. Turner Stephen M. Stick |
spellingShingle |
Angela M. Fonceca Graeme R. Zosky Elizabeth M. Bozanich Erika N. Sutanto Anthony Kicic Paul S. McNamara Darryl A. Knight Peter D. Sly Debra J. Turner Stephen M. Stick Accumulation mode particles and LPS exposure induce TLR-4 dependent and independent inflammatory responses in the lung Respiratory Research Asthma TLR-4 PM LPS AMP COPD |
author_facet |
Angela M. Fonceca Graeme R. Zosky Elizabeth M. Bozanich Erika N. Sutanto Anthony Kicic Paul S. McNamara Darryl A. Knight Peter D. Sly Debra J. Turner Stephen M. Stick |
author_sort |
Angela M. Fonceca |
title |
Accumulation mode particles and LPS exposure induce TLR-4 dependent and independent inflammatory responses in the lung |
title_short |
Accumulation mode particles and LPS exposure induce TLR-4 dependent and independent inflammatory responses in the lung |
title_full |
Accumulation mode particles and LPS exposure induce TLR-4 dependent and independent inflammatory responses in the lung |
title_fullStr |
Accumulation mode particles and LPS exposure induce TLR-4 dependent and independent inflammatory responses in the lung |
title_full_unstemmed |
Accumulation mode particles and LPS exposure induce TLR-4 dependent and independent inflammatory responses in the lung |
title_sort |
accumulation mode particles and lps exposure induce tlr-4 dependent and independent inflammatory responses in the lung |
publisher |
BMC |
series |
Respiratory Research |
issn |
1465-993X |
publishDate |
2018-01-01 |
description |
Abstract Background Accumulation mode particles (AMP) are formed from engine combustion and make up the inhalable vapour cloud of ambient particulate matter pollution. Their small size facilitates dispersal and subsequent exposure far from their original source, as well as the ability to penetrate alveolar spaces and capillary walls of the lung when inhaled. A significant immuno-stimulatory component of AMP is lipopolysaccharide (LPS), a product of Gram negative bacteria breakdown. As LPS is implicated in the onset and exacerbation of asthma, the presence or absence of LPS in ambient particulate matter (PM) may explain the onset of asthmatic exacerbations to PM exposure. This study aimed to delineate the effects of LPS and AMP on airway inflammation, and potential contribution to airways disease by measuring airway inflammatory responses induced via activation of the LPS cellular receptor, Toll-like receptor 4 (TLR-4). Methods The effects of nebulized AMP, LPS and AMP administered with LPS on lung function, cellular inflammatory infiltrate and cytokine responses were compared between wildtype mice and mice not expressing TLR-4. Results The presence of LPS administered with AMP appeared to drive elevated airway resistance and sensitivity via TLR-4. Augmented TLR4 driven eosinophilia and greater TNF-α responses observed in AMP-LPS treated mice independent of TLR-4 expression, suggests activation of allergic responses by TLR4 and non-TLR4 pathways larger than those induced by LPS administered alone. Treatment with AMP induced macrophage recruitment independent of TLR-4 expression. Conclusions These findings suggest AMP-LPS as a stronger stimulus for allergic inflammation in the airways then LPS alone. |
topic |
Asthma TLR-4 PM LPS AMP COPD |
url |
http://link.springer.com/article/10.1186/s12931-017-0701-z |
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