Comparison of mechanisms of IL-3 induced histamine release and IL-3 priming effect on human basophils

Publisher Website
Google Scholar
Abstract
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.

This publication has 43 references indexed in Scilit: