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β‐ADRENOCEPTOR‐MEDIATED INHIBITION OF MEDIATOR RELEASE FROM HUMAN PERIPHERAL BLOOD‐DERIVED MAST CELLS
Author(s) -
Wang XS,
Lau HYA
Publication year - 2006
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2006.04435.x
Subject(s) - histamine , immunoglobulin e , mast cell , prostaglandin d2 , endocrinology , chemistry , medicine , leukotriene c4 , leukotriene , isoprenaline , pharmacology , biology , prostaglandin , immunology , antibody , stimulation , asthma
SUMMARY1 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 β‐adrenoceptor subtype expressed by these cultured cells has not been identified. The aim of the present study was to characterize pharmacologically the β‐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 β‐adrenoceptor agonists or antagonist and then challenged with anti‐human IgE. The release of histamine, PGD 2 and LTC 4 from mast cells was determined. 3 Both isoprenaline and salbutamol inhibited anti‐IgE‐induced release of histamine, PGD 2 and LTC 4 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 LTC 4 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 β 3 ‐adrenoceptor agonist BRL‐37344 failed to affect anti‐IgE‐induced histamine release from cultured mast cells. 4 The selective β 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 β 1 ‐adrenoceptor antagonist atenolol (10 −6 mol/L) did not have any effect. 5 These results indicate that both isoprenaline and salbutamol act at β 2 ‐adrenoceptors to suppress IgE‐mediated mediator release from cultured human mast cells.