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The effects on bronchial epithelial mucociliary cultures of coarse, fine, and ultrafine particulate matter from an underground railway station

The effects on bronchial epithelial mucociliary cultures of coarse, fine, and ultrafine particulate matter from an underground railway station
The effects on bronchial epithelial mucociliary cultures of coarse, fine, and ultrafine particulate matter from an underground railway station
We have previously shown that underground railway particulate matter (PM) is rich in iron and other transition metals across coarse (PM10–2.5), fine (PM2.5), and quasi-ultrafine (PM0.18) fractions and is able to generate reactive oxygen species (ROS). However, there is little knowledge of whether the metal-rich nature of such particles exerts toxic effects in mucus-covered airway epithelial cell cultures or whether there is an increased risk posed by the ultrafine fraction. Monolayer and mucociliary air-liquid interface (ALI) cultures of primary bronchial epithelial cells (PBECs) were exposed to size-fractionated underground railway PM (1.1–11.1?µg/cm2) and release of lactate dehydrogenase and IL-8 was assayed. ROS generation was measured, and the mechanism of generation studied using desferrioxamine (DFX) and N-acetylcysteine (NAC). Expression of heme oxygenase-1 (HO-1) was determined by RT-qPCR. Particle uptake was studied by transmission electron microscopy. Underground PM increased IL-8 release from PBECs, but this was diminished in mucus-secreting ALI cultures. Fine and ultrafine PM generated a greater level of ROS than coarse PM. ROS generation by ultrafine PM was ameliorated by DFX and NAC, suggesting an iron-dependent mechanism. Despite the presence of mucus, ALI cultures displayed increased HO-1 expression. Intracellular PM was observed within vesicles, mitochondria, and free in the cytosol. The results indicate that, although the mucous layer appears to confer some protection against underground PM, ALI PBECs nonetheless detect PM and mount an antioxidant response. The combination of increased ROS-generating ability of the metal-rich ultrafine fraction and ability of PM to penetrate the mucous layer merits further research.
bronchial epithelium, environmental exposure, metals, particulate matter, primary cell culture, underground railway
1096-6080
98-107
Loxham, M.
8ef02171-9040-4c1d-8452-2ca34c56facb
Morgan-Walsh, R.J.
ea6539b5-a8ef-41b6-b9e3-9b715d4e1fed
Cooper, M.J.
54f7bff0-1f8c-4835-8358-71eef8529e7a
Blume, C.
aa391c64-8718-4238-906b-d6bb1551a07b
Swindle, E.J.
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Dennison, P.W.
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Howarth, P.H.
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Cassee, F.R.
e2c127c8-42b3-499c-a842-f003b82a3238
Teagle, D.A.H.
396539c5-acbe-4dfa-bb9b-94af878fe286
Palmer, M.R.
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Davies, D.E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Loxham, M.
8ef02171-9040-4c1d-8452-2ca34c56facb
Morgan-Walsh, R.J.
ea6539b5-a8ef-41b6-b9e3-9b715d4e1fed
Cooper, M.J.
54f7bff0-1f8c-4835-8358-71eef8529e7a
Blume, C.
aa391c64-8718-4238-906b-d6bb1551a07b
Swindle, E.J.
fe393c7a-a513-4de4-b02e-27369bd7e84f
Dennison, P.W.
e9c4baa7-4c64-40af-a8ad-cbc4fe7c60c2
Howarth, P.H.
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Cassee, F.R.
e2c127c8-42b3-499c-a842-f003b82a3238
Teagle, D.A.H.
396539c5-acbe-4dfa-bb9b-94af878fe286
Palmer, M.R.
d2e60e81-5d6e-4ddb-a243-602537286080
Davies, D.E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38

Loxham, M., Morgan-Walsh, R.J., Cooper, M.J., Blume, C., Swindle, E.J., Dennison, P.W., Howarth, P.H., Cassee, F.R., Teagle, D.A.H., Palmer, M.R. and Davies, D.E. (2015) The effects on bronchial epithelial mucociliary cultures of coarse, fine, and ultrafine particulate matter from an underground railway station. Toxicological Sciences, 145 (1), 98-107. (doi:10.1093/toxsci/kfv034). (PMID:25673499)

Record type: Article

Abstract

We have previously shown that underground railway particulate matter (PM) is rich in iron and other transition metals across coarse (PM10–2.5), fine (PM2.5), and quasi-ultrafine (PM0.18) fractions and is able to generate reactive oxygen species (ROS). However, there is little knowledge of whether the metal-rich nature of such particles exerts toxic effects in mucus-covered airway epithelial cell cultures or whether there is an increased risk posed by the ultrafine fraction. Monolayer and mucociliary air-liquid interface (ALI) cultures of primary bronchial epithelial cells (PBECs) were exposed to size-fractionated underground railway PM (1.1–11.1?µg/cm2) and release of lactate dehydrogenase and IL-8 was assayed. ROS generation was measured, and the mechanism of generation studied using desferrioxamine (DFX) and N-acetylcysteine (NAC). Expression of heme oxygenase-1 (HO-1) was determined by RT-qPCR. Particle uptake was studied by transmission electron microscopy. Underground PM increased IL-8 release from PBECs, but this was diminished in mucus-secreting ALI cultures. Fine and ultrafine PM generated a greater level of ROS than coarse PM. ROS generation by ultrafine PM was ameliorated by DFX and NAC, suggesting an iron-dependent mechanism. Despite the presence of mucus, ALI cultures displayed increased HO-1 expression. Intracellular PM was observed within vesicles, mitochondria, and free in the cytosol. The results indicate that, although the mucous layer appears to confer some protection against underground PM, ALI PBECs nonetheless detect PM and mount an antioxidant response. The combination of increased ROS-generating ability of the metal-rich ultrafine fraction and ability of PM to penetrate the mucous layer merits further research.

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e-pub ahead of print date: 10 February 2015
Published date: May 2015
Keywords: bronchial epithelium, environmental exposure, metals, particulate matter, primary cell culture, underground railway
Organisations: Geochemistry, Institute for Life Sciences, NIHR Southampton Respiratory Biomedical Research Unit, Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 377715
URI: https://eprints.soton.ac.uk/id/eprint/377715
ISSN: 1096-6080
PURE UUID: 6cc1ac0c-2354-47d1-8827-1d15a1d656a2
ORCID for M. Loxham: ORCID iD orcid.org/0000-0001-6459-538X
ORCID for M.J. Cooper: ORCID iD orcid.org/0000-0002-2130-2759
ORCID for C. Blume: ORCID iD orcid.org/0000-0001-6133-7318
ORCID for E.J. Swindle: ORCID iD orcid.org/0000-0003-3644-7747
ORCID for D.A.H. Teagle: ORCID iD orcid.org/0000-0002-4416-8409
ORCID for D.E. Davies: ORCID iD orcid.org/0000-0002-5117-2991

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Date deposited: 03 Jun 2015 12:40
Last modified: 17 Jul 2019 01:23

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Contributors

Author: M. Loxham ORCID iD
Author: R.J. Morgan-Walsh
Author: M.J. Cooper ORCID iD
Author: C. Blume ORCID iD
Author: E.J. Swindle ORCID iD
Author: P.W. Dennison
Author: P.H. Howarth
Author: F.R. Cassee
Author: D.A.H. Teagle ORCID iD
Author: M.R. Palmer
Author: D.E. Davies ORCID iD

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