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 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.
Dowling
R B
RB
Host Defence Unit, Imperial College of Science, Technology and Medicine, National Heart and Lung Institute, London, United Kingdom.
Rayner
C F
CF
Rutman
A
A
Jackson
A D
AD
Kanthakumar
K
K
Dewar
A
A
Taylor
G W
GW
Cole
P J
PJ
Johnson
M
M
Wilson
R
R
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
D000318:Adrenergic beta-Agonists; D000068299:Salmeterol Xinafoate; D011710:Pyocyanine; D010196:Pancreatic Elastase; D000420:Albuterol