Pharmacologic regulation of histamine release by the human recombinant histamine-releasing factor

Roy Bheekha-Escura, Stacy R. Chance, Jacqueline M. Langdon, Donald W. MacGlashan, Susan M. MacDonald

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Background: The recently cloned human recombinant IgE-dependent histamine releasing factor (HrHRF) was initially thought to stimulate histamine release from human basophils from a subpopulation of allergic donors by interacting with the IgE molecules on the surface of these cells. Additional data suggest that HrHRF exerts its biologic effects by binding to a distinct cell surface structure and not to IgE. Objective: To address the hypothesis that the HrHRF signaling pathway is distinct from the classical high-affinity IgE receptor (FcεRI) pathway, we used pharmacologic agents known to affect basophil histamine release. Methods: In this report we compared the effect of staurosporine, Bis II, Gö 6976, rottlerin, and pertussis toxin on histamine release from human basophils mediated by the following stimuli: HrHRF, polyclonal human anti-IgE antibody, and antigen, as well as the IgE-independent stimulus, FMLP. Results: None of these modulators, except rottlerin, could differentiate histamine release induced by anti-IgE or antigen from that induced by HrHRF. Rottlerin enhanced HrHRF-mediated histamine release and dose dependently blocked FMLP-mediated release without affecting basophil activation by either anti-IgE or antigen. Conclusion: These data suggest a unique signaling pathway for HrHRF and thus strengthen the hypothesis that HrHRF binds to a specific receptor other than IgE.

Original languageEnglish (US)
Pages (from-to)937-943
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume103
Issue number5 II
DOIs
StatePublished - 1999

Keywords

  • Histamine-releasing factor
  • Human basophils
  • IgE heterogeneity
  • Pharmacologic regulation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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