Azithromycin prevents airway epithelial barrier dysfunction induced by sulphur dioxide inhalation

Azithromycin (AZM) is a macrolide which is effective in the treatment of several airway diseases induced by bacterial or environmental insults. We have previously shown barrier enhancing effects of AZM on airway epithelium (AE). In order to analyze barrier enhancing effects of AZM in vivo we have challenged mice with inhalation of sulphur dioxide (SO2) to induce AE barrier failure. Mice were exposed to 50-400 ppm SO2 gas for 0.5-4 hours and monitored up to 7 days before bronchoalveolar lavage fluid (BALF) collection and analysis. AE barrier function was evaluated by measuring human serum albumin (HSA) leakage into BALF. HSA was injected into the tail vein of mice one hour prior to sacrifice, BALF was then harvested and HSA concentration measured by ELISA. AZM administered prior to exposure to SO2 resulted in a reduction of HSA, indicating protective effects of AZM on the AE. Increased intracellular vacuolization and lamellar body (LB) formations were seen in AZM treated animals. Glutathione-S-Transferases (GSTs), a class of enzymes that help maintain cellular integrity, were reduced in SO2 treated mice. Mass spectrometry analysis of BALF from SO2 exposed mice revealed that treating the mice with AZM lead to higher concentrations of GSTs in BALF, suggesting a link between AZM treatment and a reduction in GST concentration. In conclusion, we demonstrated a protective effect of AZM on the barrier integrity of the AE, possibly through stabilizing the intracellular microenvironment and by facilitating formation of LBs, providing further insight to its effectiveness in the treatment of airway diseases.