Using Reducing Agent TCEP to Alter the Rate of Mucocilliary Transport

Cystic Fibrosis (CF) as a genetic disease is characterized by a loss of function mutation in the Cystic Fibrosis transmembrane conductance regulator (CFTR). Without Chloride and Bicarbonate transduction the patient exhibits loss of host defense mechanisms and increased mucus viscosity, creating an environment that promotes chronic respiratory infection. We hypothesize that reducing agent tris(2-carboxyethyl)phosphine (TCEP) will break down intermolecular bonds within the mucus, thus increasing the rate of mucus clearance by mucociliary transport. It was shown that TCEP has no effect on the ciliary beat frequency of ethmoid epithelial cells, thus, not altering the rate of transport. In vivo computed tomography (CT) scans of non-CF pigs show a significantly increased clearance rate of microdisks applied to the airway after TCEP treatment. TCEP application caused no difference in viscosity of mucus samples with 6% and 12% mucin, but a slight decrease in the viscosity may occur with 3% mucin samples. In the future we hope to investigate these same questions using CF pig models rather than non-CF. Ease of mucus detachment has been hinted to significantly affect the rate of clearance. This research will prove important to developing newer and more effective treatments for Cystic Fibrosis.