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01.12.2018 | Research | Ausgabe 1/2018 Open Access

Respiratory Research 1/2018

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

Zeitschrift:
Respiratory Research > Ausgabe 1/2018
Autoren:
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
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12931-017-0701-z) contains supplementary material, which is available to authorized users.

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.
Zusatzmaterial
Additional file 1: Figure S1. Airway resistance in TLR4−/− mice treated with double distilled water (ddH2O) and saline. Saline responses were significantly greater for methacholine challenges larger than 3 mg/ml (* p < 0.05). (TIFF 356 kb)
12931_2017_701_MOESM1_ESM.tif
Additional file 2: Figure S2. Airway resistance in wildtype (WT) and TLR4−/− mice for all treatment groups across for all methacholine challenges used. Raw was significantly greater in WT mice treated with LPS and AMP-LPS compared to control mice at 30 mg/ml MCh (*p < 0.05). (TIFF 1196 kb)
12931_2017_701_MOESM2_ESM.tif
Additional file 3: Figure S3. Additional cytokines measured in bronchoalveolar lavage (BAL) and lung parenchyma. MCP-1 was measured in BAL using cytokine bead array assay (20-5000 pg/ml detection range) and IL-8 in lung parenchyma using ELISA (15.6-1000 pg/ml detection range) using optimised sample dilution factors. No significant difference with treatment was observed for these cytokines. (TIFF 558 kb)
12931_2017_701_MOESM3_ESM.tif
Literatur
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