Basophils from approximately one fifth of the population were found to be unresponsive (nonreleasers), in terms of both histamine and leukotriene release, to an IgE cross-linking stimulus, such as anti-IgE antibody. Although unresponsive to any IgE-mediated stimulation, these basophils responded to non-IgE-mediated stimuli, such as the phorbol ester, 12-O-tetradecanoyl phorbol-13 acetate, the calcium ionophore, A23187, and to formyl-methionyl-leucyl-phenylalanine peptide. These stimuli produced equal dose-response curves in both releaser (basophils able to respond with >5% histamine release to anti-IgE antibody) and nonreleaser basophils. Nonreleaser basophils possessed statistically similar densities of cell-surface IgE antibody (287,000 versus 400,000 IgE molecules per basophil for releaser and nonreleaser basophils, respectively), and with 12-O-tetradecanoyl phorbol-13 acetate as a probe of anti-IgE-induced cross-linking, the IgE on nonreleaser basophils was found to be cross-linked by the polyclonal anti-IgE antibody used for these studies. Interleukin-3 (IL-3) has previously been demonstrated to enhance markedly both histamine and leukotriene release in human basophils. However, IL-3 was unable to convert nonreleasing basophils into releasing basophils, as measured by anti-IgE antibody. IL-3 equivalently enhanced formyl methionine peptide-induced release in both releaser and nonreleaser basophils, suggesting that the lack of an effect on anti-IgE-induced release was not due to a lack of IL-3 receptors. Although there are several possible interpretations of these data, these results and results of our previous studies of protein kinase C activation and cytosolic Ca++ elevations in human basophils suggest that nonreleasing basophils have a defect in early signal transduction, possibly involving the influx of Ca++.
ASJC Scopus subject areas
- Immunology and Allergy