The effect of interleukin 3 upon IgE‐dependent and IgE‐independent basophil degranulation and leukotriene generation

Abstract

Recent investigations have shown that the hematopoietic growth factor interleukin 3 (IL 3) enhances histamine release of mature human basophils. Furthermore, basophils exposed to IL 3 generate large amounts of leukotriene C4 in response to C5a, a basophil agonist which by itself is unable to promote lipid mediator formation. Also IL 3 renders the cells responsive to factors which do not otherwise induce basophil mediator release. Here we show in more detail how IL 3 affects the release of preformed and newly synthesized inflammatory mediators by basophils in response to antigen, anti-IgE, N-formyl-methionyl-leucyl-phenylalanine (FMLP) and C5a. In cells triggered by maximally effective concentrations of these agonists, IL 3 enhances histamine release, although it more profoundly affects leukotriene generation, in particular in response to stimuli which by themselves are inefficient or poor inducers of lipid mediator formation. This change in the mediator-release reaction occurs at low IL 3 concentrations, over the same concentration range of IL 3 of 0.01-1.0 U/ml regardless of which triggering agent is used as a second signal. Pretreatment of basophils with IL 3 results in a left shift of the dose-response curves for mediator release of both IgE-dependent and IgE-independent agonists by approximately one order of magnitude. IL 3 affects only the extent and not the time course of IgE-independent peptide-induced basophil degranulation. By contrast, histamine and leukotrienes are released more rapidly in response to IgE-dependent stimulation after IL 3 priming. IL 3 also shortens the lag time and increases the rate of leukotriene generation in basophils triggered by FMLP. The priming process induced by IL 3 does not require extracellular calcium. Basophils exposed to IL 3 release significant amount of mediators in response to C5a, even in EDTA buffers without addition of Ca2+/Mg2+, indicating that in the presence of IL 3 the Ca2(+)-dependent mediator release induced by C5a becomes partially Ca2+ independent. Thus, we find that IL 3 strongly affects the mediator profile, the amounts of mediators released, the dose-response curves and the kinetic of the release reaction in basophils stimulated with diverse agonists. The data further support the hypothesis that IL 3 plays an important role in inflammatory processes, in particular in hypersensitivity reactions.