The epithelial cells have the capacity to absorb it through the apical membrane at an equal or higher rate. What is the driving force that allows epithelial absorption of glucose from both the apical and basolateral compartments? Our data supports interesting conclusions. Intracellular glucose, under normal conditions, is constantly phosphorylated by hexokinase in an ATP-dependent reaction, creating flux into a chemical “fourth compartment”. This would maintain an intracellular nonphosphorylated glucose concentration that is lower than that of blood, and a glucose concentration gradient that can be the driving force for basolateral uptake. Any glucose reaching the ASL would therefore be absorbed at a rate that would keep it at concentration equilibrium with intracellular non-phosphorylated glucose. Data supporting this idea come from studies performed in isolated lung cells grown in suspension, in which the intracellular concentration of glucose was found to be,0.5 mM when the extracellular glucose was 5 mM or higher. Disruption of this homeostatic mechanism could occur at different levels. An increase in blood glucose concentration, such as in diabetes mellitus, could result in an increased rate of glucose flux into ASL with correspondingly increased glucose concentration. This could explain the increased rate of ventilator-associated MRSA pneumonia in ICU patients with hyperglycemia and the poor outcomes in hyperglycemic patients hospitalized for community acquired pneumonia. This mechanism could also be disrupted by fluctuations of tight junction permeability, such as those induced by hypersensitivity reactions, exposure to toxic particles, or other inflammatory stimuli, including viral infections such as influenza or the common cold, which have been shown to increase the risk of bacterial pneumonia and correlate with detection of nasal glucose. Also, even though environmental exposures to glucose are uncommon, the presence of sugars in formulations that are nebulized into the airway could affect the homeostatic mechanism we have described. Finally, disruption of apical transport of glucose –as shown in our in vitro data– could impair generation of the glucose concentration gradient. It has been shown that mutations in the gene encoding GLUT-10 are responsible for Arterial Tortuosity Syndrome, a rare autosomal recessive disorder, with a phenotype characterized by arterial elongation, tortuosity and aneurysms, and a high mortality rate. The cause of early deaths has not been studied extensively, but a lethal case of spontaneous bilateral Staphylococcus aureus bronchopneumonia in a 4 year-old child has been reported. The question of whether this Screening Libraries infection was a consequence of impaired glucose transport in the airways remains to be answered. Bacteria constantly challenge the airways, and whether they are eliminated, resulting in a sterile lung, or proliferate to cause infection or colonization depends on host factors and the bacteria.