IL-4 and-5 prime human mast cells for different profiles of IgE-dependent cytokine production

Mast cells (MC) are stem cell factor-dependent tissue-based hematopoietic cells with substantial functional heterogeneity. Cord blood-derived human MC (hMC) express functional receptors for IL-5, and IL-5 mediates stem cell factor-dependent comitogenesis of hMC in vitro. Although IL-5 is not required for normal hMC development, we considered that it might prime hMC for their high-affinity Fc receptor for IgE (Fc epsilon RI)-dependent generation of cytokines. as previously demonstrated for IL-4. Compared with hMC maintained in stem cell factor alone, hMC primed with IL-5 expressed 2- to 4-fold higher steady-state levels of TNF-alpha, IL-5. IL-13, macrophage inflammatory protein 1 alpha, and granulocyte-macrophage colony-stimulating factor transcripts 2 h after Fc epsilon RI crosslinking and secreted 2- to 5-fold greater quantities of the corresponding cytokines, except IL-13. at 6 h. Unlike IL-4. IL-5 priming did not enhance Fc epsilon RI-dependent histamine release. Thus. IL-5 augments cytokine production by hMC by a mechanism distinct from that of IL-4 and with a different resultant profile of cytokine production. These observations suggest a potentially autocrine effect of IL-5 on hMC for amplification of allergic immune responses, in addition to its recognized paracrine effects on eosinophils, and implicate both IL-4 and IL-5 in the modulation of the hMC phenotype.