Inhibitory effect of salmeterol on the respiratory burst of adherent human neutrophils.
Human neutrophils, plated in fibronectin-coated wells and stimulated with N-formyl-methionylleucyl-phenylalanine (fMLP), were found to undergo a massive and prolonged respiratory burst, as measured by monitoring superoxide production. The beta 2-agonist salmeterol inhibited the respiratory burst in a dose-dependent manner. In contrast, salbutamol was ineffective. Moreover, the neutrophil respiratory burst was partially suppressed by prostaglandin E2 (PGE2) and the phosphodiesterase type IV (PDE-IV) inhibitor RO 20-1724. When salmeterol was used in combination with PGE2 or RO 20-1724, additive inhibitory effects were observed. The inhibitory activity of salmeterol was not reversed in the presence of the beta-blocker propranolol, and did not correlate with its ability of increasing cyclic AMP (cAMP) levels. Finally, the compounds used did not affect neutrophil adherence to fibronectin-coated wells. The results suggest that salmeterol is capable of down-regulating the neutrophil oxidative response to fMLP, also of co-operating with PGE2 and PDE-IV inhibitor RO 20-1724 in a manner not related to its beta 2-receptor binding activity. In other words, salmeterol displays neutrophil-directed effects, susceptible to be amplified by natural mediators such as PGE2 or PDE-IV inhibitors, consistent with possible anti-inflammatory properties of the drug.
Ottonello
L
L
Department of Internal Medicine, University of Genova Medical School, Italy.
Morone
P
P
Dapino
P
P
Dallegri
F
F
D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D015232:Dinoprostone / Q000502:physiology; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000502:physiology; D016897:Respiratory Burst / Q000187:drug effects* / Q000276:immunology; D000068299:Salmeterol Xinafoate
D000318:Adrenergic beta-Agonists; D000068299:Salmeterol Xinafoate; D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D015232:Dinoprostone; D000420:Albuterol