Accumulation mode particles and LPS exposure induce TLR-4 dependent and independent inflammatory responses in the lung
© 2018 The Author(s). 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...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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BIOMED CENTRAL LTD
2018
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| Online Access: | http://hdl.handle.net/20.500.11937/76775 |
| _version_ | 1848763755893096448 |
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| author | Fonceca, A.M. Zosky, G.R. Bozanich, E.M. Sutanto, E.N. Kicic, Anthony McNamara, P.S. Knight, D.A. Sly, P.D. Turner, D.J. Stick, S.M. |
| author_facet | Fonceca, A.M. Zosky, G.R. Bozanich, E.M. Sutanto, E.N. Kicic, Anthony McNamara, P.S. Knight, D.A. Sly, P.D. Turner, D.J. Stick, S.M. |
| author_sort | Fonceca, A.M. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | © 2018 The Author(s). 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. |
| first_indexed | 2025-11-14T11:08:31Z |
| format | Journal Article |
| id | curtin-20.500.11937-76775 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T11:08:31Z |
| publishDate | 2018 |
| publisher | BIOMED CENTRAL LTD |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-767752019-11-11T06:08:44Z Accumulation mode particles and LPS exposure induce TLR-4 dependent and independent inflammatory responses in the lung Fonceca, A.M. Zosky, G.R. Bozanich, E.M. Sutanto, E.N. Kicic, Anthony McNamara, P.S. Knight, D.A. Sly, P.D. Turner, D.J. Stick, S.M. Science & Technology Life Sciences & Biomedicine Respiratory System Asthma TLR-4 PM LPS AMP COPD AMBIENT PARTICULATE MATTER AIR-POLLUTION ASTHMA INHALATION MICE TOXICITY URBAN LIPOPOLYSACCHARIDE EXPRESSION ULTRAFINE © 2018 The Author(s). 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. 2018 Journal Article http://hdl.handle.net/20.500.11937/76775 10.1186/s12931-017-0701-z English http://creativecommons.org/licenses/by/4.0/ BIOMED CENTRAL LTD fulltext |
| spellingShingle | Science & Technology Life Sciences & Biomedicine Respiratory System Asthma TLR-4 PM LPS AMP COPD AMBIENT PARTICULATE MATTER AIR-POLLUTION ASTHMA INHALATION MICE TOXICITY URBAN LIPOPOLYSACCHARIDE EXPRESSION ULTRAFINE Fonceca, A.M. Zosky, G.R. Bozanich, E.M. Sutanto, E.N. Kicic, Anthony McNamara, P.S. Knight, D.A. Sly, P.D. Turner, D.J. Stick, S.M. Accumulation mode particles and LPS exposure induce TLR-4 dependent and independent inflammatory responses in the lung |
| title | 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_short | 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 |
| topic | Science & Technology Life Sciences & Biomedicine Respiratory System Asthma TLR-4 PM LPS AMP COPD AMBIENT PARTICULATE MATTER AIR-POLLUTION ASTHMA INHALATION MICE TOXICITY URBAN LIPOPOLYSACCHARIDE EXPRESSION ULTRAFINE |
| url | http://hdl.handle.net/20.500.11937/76775 |