Effect of R59022, an inhibitor of diacylglycerol kinase, on IgE-mediated histamine release from human lung mast cells and basophils

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Abstract
We have examined the effect of the diacylglycerol kinase inhibitor R59022 on histamine release from human lung mast cells and basophils. At 1 μM the drug increased the IgE-dependent release of histamine from human basophils from 19±5% to 60±13% (n=5,pM. 1 μM R59022 also increased f-met peptide-induced histamine release from 18±4% to 55±11% (n=5,pr=0.764,pM R59022. In contrast, to these potent effects on the human basophil the drug failed to affect the anti-IgE-induced release of histamine from human lung mast cells. The data suggest that the R59022 increases the release of histamine induced by anti-IgE in human basophils but not in human lung mast cells. Furthermore, the ability of R59022 to potentiate basophil histamine release is restricted to receptor-mediated stimuli such as anti-IgE and does not extend to non-physiologic stimuli such as the phorbol ester PMA.