Effect of salmeterol on Pseudomonas aeruginosa infection of respiratory mucosa

We have studied the effect of salmeterol on both P. aeruginosa interactions with the mucosa of nasal turbinate organ cultures and on pyocyanin-induced (20 mu g/ml) and elastase-induced (100 mu g/ml) damage to nasal epithelial cells. Organ cultures were exposed to salmeterol either by preincubation with 4 x 10(-7) M salmeterol for 30 min or by pipetting 20 mu l of 4 x 10(-7) M salmeterol onto the organ culture surface immediately prior to bacterial inoculation. Infected organ cultures (8 h) had significantly (p less than or equal to 0.01) increased epithelial damage, and P. aeruginosa was predominantly associated with damaged epithelium and mucus. Salmeterol significantly (p less than or equal to 0.02) reduced epithelial damage caused by infection and the total number of adherent bacteria (p less than or equal to 0.05), but bacterial distribution on the mucosa was unchanged. Nasal epithelial cells incubated with pyocyanin (20 mu g/ml) or elastase (100 mu g/ml) for 3 h had significantly (p less than or equal to 0.05) increased cytoplasmic blebbing and mitochondrial damage versus control values. Elastase also significantly (p less than or equal to 0.05) increased cell projection and reduced the revel of ciliation. Cells preincubated with salmeterol (2 x 10(-7) M) showed a significant reduction in some features of cell damage caused by both toxins, which was inhibited by the beta(2)-adrenoceptor antagonist propranolol. Our results indicate that salmeterol reduces P. aeruginosa-induced damage to both organ culture and nasal epithelium.