EFFECT OF R59022, AN INHIBITOR OF DIACYLGLYCEROL KINASE, ON IGE-MEDIATED HISTAMINE-RELEASE FROM HUMAN LUNG MAST-CELLS AND BASOPHILS

We have examined the effect of the diacylglycerol kinase inhibitor R59 022 on histamine release from human lung mast cells and basophils. At 1 mu M the drug increased the IgE-dependent release of histamine from human basophils from 19 +/- 5% to 60 +/- 13%(n = 5, p < 0.01). The inc rease in histamine release was dose dependent with maximum enhancement between 1 and 10 mu M. 1 mu M R59022 also increased f-met peptide-ind uced histamine release from 18 +/- 4% to 55 +/- 11% (n = 5, p < 0.05). However, the drug did not significantly increase the release of hista mine when the non-physiologic stimulus PMA was used to initiate releas e. The effect of the drug on anti-IgE-induced release was most marked at lower concentrations of anti-IgE and declined when superoptimal con centrations of anti-IgE were used. As anticipated there was a strong n egative correlation (r = 0.764, p < 0.05) between anti-IgE-induced his tamine release and the percentage enhancement in the presence of 10 mu M R59022. In contrast, to these potent effects on the human basophil the drug failed to affect the anti-IgE-induced release of histamine fr om human lung mast cells. The data suggest that the R59022 increases t he release of histamine induced by anti-IgE in human basophils but not in human lung mast cells. Furthermore, the ability of R59022 to poten tiate basophil histamine release is restricted to receptor-mediated st imuli such as anti-IgE and does not extend to non-physiologic stimuli such as the phorbol ester PMA.