Pharmacologic regulation of histamine release by the human recombinant histamine-releasing factor.
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 (FcepsilonRI) 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.


CONCLUSIONS
These data suggest a unique signaling pathway for HrHRF and thus strengthen the hypothesis that HrHRF binds to a specific receptor other than IgE.
D000098:Acetophenones / Q000494:pharmacology; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001491:Basophils / Q000378:metabolism; D001578:Benzopyrans / Q000494:pharmacology; D014408:Biomarkers, Tumor; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002227:Carbazoles / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007073:Immunoglobulin E / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008222:Lymphokines / Q000494:pharmacology*; D037342:Pertussis Toxin; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology; D000090324:Tumor Protein, Translationally-Controlled 1; D010566:Virulence Factors, Bordetella / Q000494:pharmacology