Garnett, JP; Kalsi, KK; Sobotta, M; Bearham, J; Carr, G; Powell, J; Brodlie, M; Ward, C; Tarran, R; Baines, DL
(2016)
Hyperglycaemia and Pseudomonas aeruginosa acidify cystic fibrosis airway surface liquid by elevating epithelial monocarboxylate transporter 2 dependent lactate-H⁺ secretion.
Scientific Reports, 6 (37955).
ISSN 2045-2322
https://doi.org/10.1038/srep37955
SGUL Authors: Baines, Deborah
Abstract
The cystic fibrosis (CF) airway surface liquid (ASL) provides a nutrient rich environment for bacterial growth including elevated glucose, which together with defective bacterial killing due to aberrant HCO3− transport and acidic ASL, make the CF airways susceptible to colonisation by respiratory pathogens such as Pseudomonas aeruginosa. Approximately half of adults with CF have CF related diabetes (CFRD) and this is associated with increased respiratory decline. CF ASL contains elevated lactate concentrations and hyperglycaemia can also increase ASL lactate. We show that primary human bronchial epithelial (HBE) cells secrete lactate into ASL, which is elevated in hyperglycaemia. This leads to ASL acidification in CFHBE, which could only be mimicked in non-CF HBE following HCO3− removal. Hyperglycaemia-induced changes in ASL lactate and pH were exacerbated by the presence of P. aeruginosa and were attenuated by inhibition of monocarboxylate lactate-H+ co-transporters (MCTs) with AR-C155858. We conclude that hyperglycaemia and P. aeruginosa induce a metabolic shift which increases lactate generation and efflux into ASL via epithelial MCT2 transporters. Normal airways compensate for MCT-driven H+ secretion by secreting HCO3−, a process which is dysfunctional in CF airway epithelium leading to ASL acidification and that these processes may contribute to worsening respiratory disease in CFRD.
Item Type: |
Article
|
Additional Information: |
© The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images
or other third party material in this article are included in the article’s Creative Commons license,
unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license,
users will need to obtain permission from the license holder to reproduce the material. To view a copy of this
license, visit http://creativecommons.org/licenses/by/4.0/ |
SGUL Research Institute / Research Centre: |
Academic Structure > Infection and Immunity Research Institute (INII) |
Journal or Publication Title: |
Scientific Reports |
ISSN: |
2045-2322 |
Dates: |
Date | Event |
---|
2 November 2016 | Accepted | 29 November 2016 | Published |
|
Publisher License: |
Creative Commons: Attribution 4.0 |
Projects: |
|
URI: |
https://openaccess.sgul.ac.uk/id/eprint/108424 |
Publisher's version: |
https://doi.org/10.1038/srep37955 |
Statistics
Item downloaded times since 29 Nov 2016.
Actions (login required)
![Edit Item](/style/images/action_view.png) |
Edit Item |