title: Effect of salmeterol on Pseudomonas aeruginosa infection of respiratory mucosa.
abstract: 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 microg/ml) and elastase-induced (100 microg/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 microl 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 < or = 0.01) increased epithelial damage, and P. aeruginosa was predominantly associated with damaged epithelium and mucus. Salmeterol significantly (p < or = 0.02) reduced epithelial damage caused by infection and the total number of adherent bacteria (p < or = 0.05), but bacterial distribution on the mucosa was unchanged. Nasal epithelial cells incubated with pyocyanin (20 microg/ml) or elastase (100 microg/ml) for 3 h had significantly (p < or = 0.05) increased cytoplasmic blebbing and mitochondrial damage versus control values. Elastase also significantly (p < or = 0.05) increased cell projection and reduced the level 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 beta2-adrenoceptor antagonist propranolol. Our results indicate that salmeterol reduces P. aeruginosa-induced damage to both organ culture and nasal epithelium.
authors.affiliation: Host Defence Unit, Imperial College of Science, Technology and Medicine, National Heart and Lung Institute, London, United Kingdom.
authors.forename: R B
authors.initials: RB
authors.lastname: Dowling
authors.forename: C F
authors.initials: CF
authors.lastname: Rayner
authors.forename: A
authors.initials: A
authors.lastname: Rutman
authors.forename: A D
authors.initials: AD
authors.lastname: Jackson
authors.forename: K
authors.initials: K
authors.lastname: Kanthakumar
authors.forename: A
authors.initials: A
authors.lastname: Dewar
authors.forename: G W
authors.initials: GW
authors.lastname: Taylor
authors.forename: P J
authors.initials: PJ
authors.lastname: Cole
authors.forename: M
authors.initials: M
authors.lastname: Johnson
authors.forename: R
authors.initials: R
authors.lastname: Wilson
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D046508:Culture Techniques; D006801:Humans; D008854:Microscopy, Electron; D009297:Nasal Mucosa / Q000187:drug effects* / Q000382:microbiology*; D010196:Pancreatic Elastase / Q000633:toxicity; D011552:Pseudomonas Infections / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development; D011710:Pyocyanine / Q000633:toxicity; D000068299:Salmeterol Xinafoate
chemical_list: D000318:Adrenergic beta-Agonists; D000068299:Salmeterol Xinafoate; D011710:Pyocyanine; D010196:Pancreatic Elastase; D000420:Albuterol