Comparison of mechanisms of IL-3 induced histamine release and IL-3 priming effect on human basophils
Article first published online: 27 APR 2006
Clinical & Experimental Allergy
Volume 23, Issue 11, pages 901–910, November 1993
How to Cite
OKAYAMA, Y., BEGISHVILI, T. B. and CHURCH, M. K. (1993), Comparison of mechanisms of IL-3 induced histamine release and IL-3 priming effect on human basophils. Clinical & Experimental Allergy, 23: 901–910. doi: 10.1111/j.1365-2222.1993.tb00274.x
- Issue published online: 27 APR 2006
- Article first published online: 27 APR 2006
- Submitted 9 July 1992; revised 28 May 1993; accepted 10 June 1993.
We have investigated the mechanisms by which inlerleukin-3 (IL-3) induces histamine release and primes basophils for increased hislamine 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 hislamine 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 μg/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.