Differences in functional consequences and signal transduction induced by IL-3, IL-5, and nerve growth factor in human basophils

Previous studies have indicated a redundancy in the effects of the cytokine s, IL-3, IL-5, and nerve growth factor (NGF) on acute priming of human baso phils. In the current study, we have examined the effects of these three cy tokines on 18-h priming for leukotriene C4 generation, their ability to ind uce Fc epsilon RI beta mRNA expression, or their ability to sustain basophi l viability in culture. We also examine a variety of the signaling steps th at accompany activation with these cytokines. In contrast with the ability of IL-3 to alter secretagogue-mediated cytosolic calcium responses followin g 18-h cultures, 18-h treatment with IL-5 or NGF did not affect C5a-induced leukotriene C4 generation or alter C5a-induced intracellular Ca2+ concentr ation elevations. IL-3 and IL-5, but not NGF, induced Fc epsilon RI beta mR NA expression and all three improved basophil viability in culture with a r anking of IL-3 > IL-5 greater than or equal to NGF. All three cytokines acu tely activated the extracellular signal-regulated kinase pathway and the si gnaling elements that preceded extracellular signal-regulated kinase and cy tosolic phospholipase A(2) phosphorylation, consistent with their redundant ability to acutely prime basophils. However, only IL-3 and IL-5 induced Ja nus kinase 2 and STAT5 phosphorylation. This pattern of signal element acti vation among the three cytokines most closely matched their ability to indu ce expression of Fc epsilon RI beta mRNA. Induction of the sustained calciu m signaling that follows overnight priming with IL-3 appeared to be related to the strength of the early signals activated by these cytokines but the relevant pathway required was not identified. None of the signaling pattern s matched the ability of the cytokines to promote basophil survival.