A comparative study of releasing and nonreleasing human basophils: nonreleasing basophils lack an early component of the signal transduction pathway that follows IgE cross-linking.
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 greater than 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++.
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224.
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Nguyen
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Gillis
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MacGlashan
D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001491:Basophils / Q000187:drug effects / Q000378:metabolism*; D004306:Dose-Response Relationship, Immunologic; D006636:Histamine Release; D006801:Humans; D007073:Immunoglobulin E / Q000235:genetics / Q000276:immunology; D007377:Interleukin-3 / Q000494:pharmacology; D014161:Transduction, Genetic
D000888:Antibodies, Anti-Idiotypic; D007377:Interleukin-3; C026408:anti-IgE antibodies; D007073:Immunoglobulin E