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

R. Bheekha-Escura, S. R. Chance, J. M. Langdon, Donald Macglashan, Susan M MacDonald

Research output: Contribution to journalArticle

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, Go 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
JournalThe Journal of Allergy and Clinical Immunology
Volume103
Issue number5 I
DOIs
StatePublished - 1999

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Histamine Release
Basophils
Immunoglobulin E
IgE Receptors
Antigens
translationally-controlled 1 tumor protein
Staurosporine
Pertussis Toxin

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Pharmacologic regulation of histamine release by the human recombinant histamine-releasing factor. / Bheekha-Escura, R.; Chance, S. R.; Langdon, J. M.; Macglashan, Donald; MacDonald, Susan M.

In: The Journal of Allergy and Clinical Immunology, Vol. 103, No. 5 I, 1999, p. 937-943.

Research output: Contribution to journalArticle

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