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

Kim Lien Nguyen, Steven Gillis, Donald W. MacGlashan

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

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++.

Original languageEnglish (US)
Pages (from-to)1020-1029
Number of pages10
JournalThe Journal of allergy and clinical immunology
Volume85
Issue number6
DOIs
StatePublished - Jun 1990

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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