INHIBITORY EFFECT OF SALMETEROL ON THE RESPIRATORY BURST OF ADHERENT HUMAN NEUTROPHILS

Human neutrophils, plated in fibronectin-coated wells and stimulated w ith N-formyl-methionyl-leucyl-phenplalanine (fMLP), were found to unde rgo a massive and prolonged respiratory burst, as measured by monitori ng 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 parti ally suppressed by prostaglandin E(2) (PGE(2)) and the phosphodiestera se type IV (PDE-IV) inhibitor RO 20-1724. When salmeterol was used in combination with PGE(2) or RO 20-1724, additive inhibitory effects wer e observed. The inhibitory activity of salmeterol was not reversed in the presence of the beta-blocker propranolol, and did not correlate wi th its ability of increasing cyclic AMP (cAMP) levels. Finally, the co mpounds used did not affect neutrophil adherence to fibronectin-coated wells. The results suggest that salmeterol is capable of down-regulat ing the neutrophil oxidative response to fMLP, also of co-operating wi th PGE(2) and PDE-IV inhibitor RO 20-1724 in a manner not related to i ts beta(2)-receptor binding activity. In other words, salmeterol displ ays neutrophil-directed effects, susceptible to be amplified by natura l mediators such as PGE(2) or PDE-IV inhibitors, consistent with possi ble anti-inflammatory properties of the drug.