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.

Bacteria, antibiotics and COPD

“…A series of elegant experiments by Flak & Goldman [59] have shown that TCT and LPS trigger the production of IL-1, which in turn stimulates NO production that causes cell damage. The present authors have shown that inhibition of NO synthase reduced the amount of epithelial damage caused by P. aeruginosa infection of a respiratory tissue organ culture, suggesting that the mechanism elucidated for TCT might be common to other respiratory pathogens that damage epithelial cells [60]. It is, therefore, of interest that levels of exhaled NO are elevated during exacerbations of COPD, and were not reduced acutely by intravenous corticosteroids, but did return to normal several months later when the patient was clinically stable [61].…”

Downregulation by a long-acting β2-adrenergic receptor agonist and corticosteroid of Staphylococcus aureus-induced airway epithelial inflammatory mediator production

“…Salmeterol hydroxynaphthoate (Sal), a generous gift from GlaxoSmithKline (Uxbridge, UK), was dissolved in a minimum amount of glacial acetic acid (30 l), then diluted at a concentration of 2 ϫ 10 Ϫ4 M in phosphate-buffered saline (PBS), and kept at Ϫ20°C. The stock solution was used at a final concentration of 2 ϫ 10 Ϫ7 M in DMEM/F-12 previously defined as optimal for inducing airway epithelial cytoprotection (12). Solutions were buffered to a pH of 7.4.…”

Impact of cigarette smoke exposure on host-bacterial pathogen interactions

“…in urinary tract infections caused by uropathogenic Escherichia coli [132]. The PDE4 inhibitor rolipram has also shown to be effective in preventing P. aeruginosa-induced epithelial damage [133]. Also, PDE4 inhibition seems to impair host defense to Klebsiella pneumoniae infection in the pneumonia mouse model [134].…”