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

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K L O'Keefe, J A Warner

Abstract

We have examined the effect of the diacylglycerol kinase inhibitor R59022 on histamine release from human lung mast cells and basophils. At 1 microM the drug increased the IgE-dependent release of histamine from human basophils from 19 +/- 5% to 60 +/- 13% (n = 5, p < 0.01). The increase in histamine release was dose dependent with maximum enhancement between 1 and 10 microM. 1 microM R59022 also increased f-met peptide-induced histamine release from 18 +/- 4% to 55 +/- 11% (n = 5, p < 0.05). However, the drug did not significantly increase the release of histamine when the non-physiologic stimulus PMA was used to initiate release. The effect of the drug on anti-IgE-induced release was most marked at lower concentrations of anti-IgE and declined when superoptimal concentrations of anti-IgE were used. As anticipated there was a strong negative correlation (r = 0.764, p < 0.05) between anti-IgE-induced histamine release and the percentage enhancement in the presence of 10 microM 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 h...Continue Reading

References

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Citations

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Nov 20, 1998·MCN. the American Journal of Maternal Child Nursing·G Newshan, M J Hoyt
May 8, 2001·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·S WalmsleyS Richardson
Oct 15, 2003·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·A C HesselingR M Warren
Nov 12, 2002·Social Work in Health Care·David L StrugNancy L Beckerman
Aug 9, 2007·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Linda AurpibulVirat Sirisanthana
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