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Lookup NU author(s): Dr James Garnett, Erin Baker
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The glucose concentration of the airway surface liquid (ASL) is much lower than that in blood and is tightly regulated by the airway epithelium. ASL glucose is elevated in patients with viral colds, cystic fibrosis, chronic obstructive pulmonary disease, and asthma. Elevated ASL glucose is also associated with increased incidence of respiratory infection. However, the mechanism by which ASL glucose increases under inflammatory conditions is unknown. The aim of this study was to investigate the effect of proinflammatory mediators (PIMs) on the mechanisms governing airway glucose homeostasis in polarized monolayers of human airway (H441) and primary human bronchial epithelial (HBE) cells. Monolayers were treated with TNF-α, IFN-γ, and LPS during 72 h. PIM treatment led to increase in ASL glucose concentration and significantly reduced H441 and HBE transepithelial resistance. This decline in transepithelial resistance was associated with an increase in paracellular permeability of glucose. Similar enhanced rates of paracellular glucose flux were also observed across excised trachea from LPS-treated mice. Interestingly, PIMs enhanced glucose uptake across the apical, but not the basolateral, membrane of H441 and HBE monolayers. This increase was predominantly via phloretin-sensitive glucose transporter (GLUT)-mediated uptake, which coincided with an increase in GLUT-2 and GLUT-10 abundance. In conclusion, exposure of airway epithelial monolayers to PIMs results in increased paracellular glucose flux, as well as apical GLUT-mediated glucose uptake. However, uptake was insufficient to limit glucose accumulation in ASL. To our knowledge, these data provide for the first time a mechanism to support clinical findings that ASL glucose concentration is increased in patients with airway inflammation.
Author(s): Garnett JP, Nguyen TT, Moffatt JD, Pelha ER, Kalsi KK, Baker EH, Baines DL
Publication type: Article
Publication status: Published
Journal: The Journal of Immunology
Year: 2012
Volume: 189
Issue: 1
Pages: 373-380
Print publication date: 01/07/2012
Online publication date: 23/05/2012
Acceptance date: 20/04/2012
ISSN (print): 0022-1767
ISSN (electronic): 1550-6606
Publisher: American Association of Immunologists
URL: http://dx.doi.org/10.4049/jimmunol.1200718
DOI: 10.4049/jimmunol.1200718
PubMed id: 22623330
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