Airway epithelia regulate airway surface liquid glucose concentration

Abstract

The airway epithelium is lined by a small amount of airway surface liquid (ASL). Studies of exhaled breath condensate suggest that this liquid has a low glucose concentration. We investigated the mechanism that maintains a transepithelial glucose gradient in well‐differentiated human airway epithelia (HAE) grown at the air‐liquid interface. We found that HAE do not have electrogenic glucose transport, suggesting absence of sodium‐glucose cotransporters (SGLT). Polarized HAE cultures maintained a glucose gradient with low apical levels. In bidirectional flux assays, we found that HAE have low paracellular permeability to L‐glucose. Moreover, 2‐deoxyglucose fluxes favored basal to apical transport. Immunofluorescence showed that the facilitated diffusion transporter GLUT‐1 is expressed in the basolateral membrane and GLUT‐10 is expressed in the apical membrane. Finally, we found that increasing ASL glucose results in increased infection with P. aeruginosa in vitro and in vivo. These data suggest that either increased serum glucose concentration or disruption of the paracellular barrier could result in increased glucose in the ASL and increased risk of pulmonary infection.