Immunopharmacological studies on human mast cells and basophils

The aims of this project were first to investigate the extent to which drugs used for the treatment of allergic diseases may have an effect on the early phase of IgE-dependent mast cell activation. Second, as IL-3, some eosinophil granule proteins and histamine-releasing factors are considered to initiate basophil activation in the late phase of allergic reaction, the effect of these agents on histamine release from human mast cells was investigated. Third, the production of cytokines by human mast cells was investigated. High concentrations of sodium cromoglycate, nedocromil sodium and antihistamines were required to significantly inhibit IgE-dependent release of histamine and PGD2 from mast cells. There was some heterogeneity observed for mast cells from different human tissues in the degree of pharmacological control by these agents. In contrast, nanomolar concentrations of β-adrenoceptor agonists consistently inhibited histamine and PGD_2 release. IL-3, eosinophil granule proteins and peripheral blood mononuclear cell-derived histamine-releasing factors neither induced nor primed IgE-dependent histamine release from human mast cells. As a part of these studies, the mechanisms of activation of basophils by IL-3 were investigated. Histamine release by IL-3 required both extracellular Ca^2+ and the presence of membrane IgE, but IL-3 priming did not. The activation of stem cell factor-primed mast cells via Fc_6RI, induced expression of IL-4 and IL-5 mRNA at time points ranging from 2 to 24 h and 2 to 72 h, respectively. In conclusion, (1) antiallergic drugs are weak inhibitors of histamine and PGD_2 release from mast cells in vitro; (2) several basophil priming factors are without effect on the functional activity of mast cells; (3) human mast cells may contribute to the chronicity of tissue inflammation by the production of cytokines.