Inhibitory effect of salmeterol on the respiratory burst of adherent human neutrophils

Abstract

Human neutrophils, plated in fibronectin-coated wells and stimulated with n-formyl-methionyl-leucyl-phenylalanine (fMLP), were found to undergo a massive and prolonged respiratory burst, as measured by monitoring superoxide production. The β₂-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 β-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 β₂-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.

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