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

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Foneca, AM, Zosky, GR ORCID: 0000-0001-9039-0302, Bozanich, EM, Sutanto, EN, Kicic, A, McNamara, PS, Knight, DA, Sly, PD, Turner, DJ and Stick, SM 2018 , 'Accumulation mode particles and LPS exposure induce TLR-4 dependent and independent inflammatory responses in the lung' , Respiratory research, vol. 19, no. 1 , doi: 10.1186/s12931-017-0701-z.

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Abstract

Background: Accumulation mode particles (AMP) are formed from engine combustion and make up the inhalablevapour cloud of ambient particulate matter pollution. Their small size facilitates dispersal and subsequent exposurefar from their original source, as well as the ability to penetrate alveolar spaces and capillary walls of the lung wheninhaled. A significant immuno-stimulatory component of AMP is lipopolysaccharide (LPS), a product of Gram negativebacteria breakdown. As LPS is implicated in the onset and exacerbation of asthma, the presence or absence of LPS inambient 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 airwaysdisease by measuring airway inflammatory responses induced via activation of the LPS cellular receptor, Toll-like receptor4 (TLR-4).Methods: The effects of nebulized AMP, LPS and AMP administered with LPS on lung function, cellular inflammatoryinfiltrate 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 viaTLR-4. Augmented TLR4 driven eosinophilia and greater TNF-α responses observed in AMP-LPS treated mice independentof TLR-4 expression, suggests activation of allergic responses by TLR4 and non-TLR4 pathways larger than those inducedby 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 thenLPS alone.

Item Type: Article
Authors/Creators: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
Keywords: LPS, TLR4, lung inflammation
Journal or Publication Title: Respiratory research
Publisher: BioMed Central Ltd.
ISSN: 1465-9921
DOI / ID Number: 10.1186/s12931-017-0701-z
Copyright Information:

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

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