Journal article
Glucose Depletion in the Airway Surface Liquid Is Essential for Sterility of the Airways
PloS one, Vol.6(1), pp.e16166-e16166
2011
DOI: 10.1371/journal.pone.0016166
PMCID: PMC3029092
PMID: 21311590
Abstract
Diabetes mellitus predisposes the host to bacterial infections. Moreover, hyperglycemia has been shown to be an independent risk factor for respiratory infections. The luminal surface of airway epithelia is covered by a thin layer of airway surface liquid (ASL) and is normally sterile despite constant exposure to bacteria. The balance between bacterial growth and killing in the airway determines the outcome of exposure to inhaled or aspirated bacteria: infection or sterility. We hypothesized that restriction of carbon sources –including glucose– in the ASL is required for sterility of the lungs. We found that airway epithelia deplete glucose from the ASL via a novel mechanism involving polarized expression of GLUT-1 and GLUT-10, intracellular glucose phosphorylation, and low relative paracellular glucose permeability in well-differentiated cultures of human airway epithelia and in segments of airway epithelia excised from human tracheas. Moreover, we found that increased glucose concentration in the ASL augments growth of
P. aeruginosa in vitro
and in the lungs of hyperglycemic
ob/ob
and
db/db
mice
in vivo
. In contrast, hyperglycemia had no effect on intrapulmonary bacterial growth of a
P. aeruginosa
mutant that is unable to utilize glucose as a carbon source. Our data suggest that depletion of glucose in the airway epithelial surface is a novel mechanism for innate immunity. This mechanism is important for sterility of the airways and has implications in hyperglycemia and conditions that result in disruption of the epithelial barrier in the lung.
Details
- Title: Subtitle
- Glucose Depletion in the Airway Surface Liquid Is Essential for Sterility of the Airways
- Creators
- Alejandro A Pezzulo - University of Pittsburgh, United States of AmericaJeydith Gutiérrez - University of Pittsburgh, United States of AmericaKelly S Duschner - University of Pittsburgh, United States of AmericaKelly S McConnell - University of Pittsburgh, United States of AmericaPeter J Taft - University of Pittsburgh, United States of AmericaSarah E Ernst - University of Pittsburgh, United States of AmericaTimothy L Yahr - University of Pittsburgh, United States of AmericaKamal Rahmouni - University of Pittsburgh, United States of AmericaJulia Klesney-Tait - University of Pittsburgh, United States of AmericaDavid A Stoltz - University of Pittsburgh, United States of AmericaJoseph Zabner - University of Pittsburgh, United States of America
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.6(1), pp.e16166-e16166
- DOI
- 10.1371/journal.pone.0016166
- PMID
- 21311590
- PMCID
- PMC3029092
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library of Science; San Francisco, USA
- Alternative title
- Airway Glucose and Innate Immunity
- Language
- English
- Date published
- 2011
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Microbiology and Immunology; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984001204302771
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