INHIBITORY ACTIONS OF SALMETEROL ON HUMAN AIRWAY MACROPHAGES AND BLOOD MONOCYTES

The effect of beta(2)-adrenoceptor agonists, salmeterol and salbutamol on thromboxane B-2 release from human airway macrophages and peripheral blood monocytes has been examined. Salbutamol (0.1-100 mu M) had no inhibitory effect on the release of thromboxane B-2 from human airway macrophages. Salmeterol (0.1-100 mu M) caused dose-dependent inhibition of thromboxane B-2 release from human airway macrophages stimulated by either zymosan or calcium ionophore A23187. This inhibition was not blocked by propranolol (1 mu M). The activity of adenylyl cyclase in homogenates of human airway macrophages was increased by NaF (10 mM) by 8.5-fold and salmeterol (100 mu M) and isoprenaline (10 mu M) by 1.6- and 1.4-fold, respectively. Isoprenaline alone was inhibited by propranolol (1 mu M). Salmeterol caused a biphasic inhibition of peripheral blood monocyte thromboxane B-2 release. The inhibition at low (10 nM) concentrations of salmeterol was blocked by propranolol and that at higher concentrations (100 mu M) was unaffected. The long lipophilic tail of salmeterol had similar inhibitory effects on the airway macrophages to salmeterol itself, and on the peripheral blood monocytes its action resembled that of the highest concentrations of salmeterol used. It is concluded that salmeterol inhibits mediator release from human airway macrophages by a beta-adrenoceptor independent mechanism and from brood monocytes by both beta-adrenoceptor and non-beta-adrenoceptor mechanisms. The latter mechanism may be associated with the lipophilic properties of the salmeterol molecule.