β-adrenoceptor-mediated inhibition of mediator release from human peripheral blood-derived mast cells

1. Mast cells cultured from human peripheral blood have been used as a cell model for functional studies of human mast cells, particularly human lung mast cells. However, the beta-adrenoceptor subtype expressed by these cultured cells has not been identified. The aim of the present study was to characterize pharmacologically the beta-adrenoceptors involved in the suppression of IgE-mediated release of mediators, including histamine, prostaglandin (PG) D-2 and leukotriene (LT) C-4 from cultured mast cells. 2. Mast cells were cultured from mast cell progenitors isolated from peripheral blood in the presence of 200 ng/mL stem cell factor and 50 ng/mL interleukin-6. Mast cells were sensitized with human myeloma IgE, treated with beta-adrenoceptor agonists or antagonist and then challenged with anti-human IgE. The release of histamine, PGD(2) and LTC4 from mast cells was determined. 3. Both isoprenaline and salbutamol inhibited anti-IgE-induced release of histamine, PGD(2) and LTC4 from cultured mast cells in a dose-dependent manner. Isoprenaline was a more potent inhibitor than salbutamol. The pD(2) values for the inhibition of the release of histamine, PGD(2) and LTC4 were 7.37 +/- 0.12, 8.38 +/- 0.23, 8.85 +/- 0.23, respectively, for isoprenaline and 6.96 +/- 0.12, 7.65 +/- 0.36, 7.91 +/- 0.64, respectively, for salbutamol. The selective beta(3)-adrenoceptor agonist BRL-37344 failed to affect anti-IgE-induced histamine release from cultured mast cells. 4 .The selective beta(2)-adrenoceptor antagonist ICI 118 551 (10(-8) mol/L) strongly reversed the concentration-dependent suppression of histamine release by isoprenaline and salbutamol; however, the selective beta(1)-adrenoceptor antagonist atenolol (10(-6) mol/L) did not have any effect. 5. These results indicate that both isoprenaline and salbutamol act at beta(2)-adrenoceptors to suppress IgE-mediated mediator release from cultured human mast cells.