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Accumulation mode particles and LPS exposure induce TLR-4 dependent and independent inflammatory responses in the lung

Citation

Foneca, AM and Zosky, GR and Bozanich, EM and Sutanto, EN and Kicic, A and McNamara, PS and Knight, DA and Sly, PD and Turner, DJ and Stick, SM, Accumulation mode particles and LPS exposure induce TLR-4 dependent and independent inflammatory responses in the lung, Respiratory research, 19, (1) ISSN 1465-9921 (2018) [Refereed Article]


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Copyright 2018 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

DOI: doi:10.1186/s12931-017-0701-z

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.

Item Details

Item Type:Refereed Article
Keywords:LPS, TLR4, lung inflammation
Research Division:Medical and Health Sciences
Research Group:Cardiorespiratory Medicine and Haematology
Research Field:Respiratory Diseases
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Respiratory System and Diseases (incl. Asthma)
Author:Zosky, GR (Associate Professor Graeme Zosky)
ID Code:125425
Year Published:2018
Deposited By:Medicine (Discipline)
Deposited On:2018-04-17
Last Modified:2018-06-07
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