Comparison of mechanisms of IL-3 induced histamine release and IL-3 priming effect on human basophils.
We have investigated the mechanisms by which interleukin-3 (IL-3) induces histamine release and primes basophils for increased histamine release in response to anti-IgE- and N-formyl-methionyl-leucyl-phenylalanine (fMLP). The responsiveness of basophils from atopic donors was variable, only 5/11 subjects showing release of > 10%, to IL-3 in the range 0.1-100 ng/ml. IL-3-induced histamine release required both extracellular Ca2+ and cell membrane IgE, removal of membrane IgE by lactate stripping or desensitization of basophils by incubation with anti-IgE in a Ca2+-free medium blocking IL-3-induced histamine release. IL-3 also primed basophils for histamine release by anti-IgE and fMLP in the same concentration range as it evoked histamine release. When IL-3 and either anti-IgE or fMLP were combined, the result was additive or supra-additive depending on the basophil donor. Unlike IL-3-evoked histamine release, IL-3 priming of basophils for fMLP-induced histamine release was shown to be independent of the presence of both cell surface IgE and of extracellular calcium. The protein kinase C (PKC) inhibitor, staurosporine (10 nM), inhibited anti-IgE induced histamine release, but neither IL-3 induced histamine release nor IL-3 priming of IgE- and fMLP-induced histamine release. Pertussis toxin (1.0 microg/ml) inhibited fMLP-induced histamine release but not anti-IgE-induced histamine release, IL-3-evoked histamine release or IL-3 priming. These results indicate that IL-3 modulates mediator release from human basophils by two mechanisms; a direct release of histamine which involves cell surface IgE and the influx of extracellular calcium but which is unlikely to proceed by the same mechanism as cross-linkage of IgE, and a priming effect which is independent of IgE and extracellular Ca2+ and which enhances the secretory effects of a wide range of unrelated secretagogues.
Okayama
Y
Y
Immunopharmacology Group, Clinical Pharmacology and Medicine, Southampton General Hospital, UK.
Begishvili
T B
TB
Church
M K
MK
D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000494:pharmacology; D015549:Basophil Degranulation Test; D001491:Basophils / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000473:pathology; D007073:Immunoglobulin E / Q000187:drug effects / Q000276:immunology; D007377:Interleukin-3 / Q000008:administration & dosage / Q000494:pharmacology*; D019344:Lactic Acid / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D037342:Pertussis Toxin; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000187:drug effects / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000888:Antibodies, Anti-Idiotypic; D004791:Enzyme Inhibitors; D007377:Interleukin-3; D011947:Receptors, Antigen, B-Cell; D010566:Virulence Factors, Bordetella; C026408:anti-IgE antibodies; D019344:Lactic Acid; D007073:Immunoglobulin E; D009240:N-Formylmethionine Leucyl-Phenylalanine; D037342:Pertussis Toxin; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D019311:Staurosporine; D002118:Calcium