Human mast cells produce IL-13 by high-affinity IgE receptor cross-linking: Enhanced IL-13 production by IL-4–primed human mast cells

Abstract

Background: Mast cells play a central role not only in the early phase of the allergic reaction, but also participate in the late phase of the allergic reaction through the allergen and IgE-dependent release of multifunctional cytokines. Objective: Using the recently established culture system for human mast cells, we examined the expression of a variety of cytokines in cord blood–derived human cultured mast cells (HCMCs) in response to different stimuli. Methods: HCMCs were grown from cord blood mononuclear cells in the presence of stem cell factor and IL-6 for 10 weeks. Cytokine mRNA expression in HCMCs by the different stimuli was examined by RT-PCR. Then taking 2 important cytokines, IL-13 and IL-4, that share several functional properties and play important roles in allergic diseases, we examined protein as well as mRNA expression of both cytokines in HCMCs. Results: HCMCs did not express either IL-13 or IL-4 spontaneously. Stimulation with PMA + A23187 induced the expression of IL-4 protein, as well as IL-13 protein, in their cytoplasm, although IL-4 secreted in the supernatant was below detectable levels in contrast to a significant amount of IL-13. Stimulation of HCMCs by cross-linking of the high-affinity IgE receptor (FcϵRI) induced the expression of IL-13 mRNA and protein, but not IL-4. Although we previously found that IL-4 upregulates FcϵRI expression on HCMCs, when HCMCs were first cultured in the presence of IL-4 and then activated through FcϵRI cross-linking, remarkable increase was found in IL-13 production. Furthermore, although IL-4 was still undetectable at protein level, IL-4 mRNA expression was induced in the IL-4–primed HCMCs stimulating FcϵRI cross-linking. In addition, we examined the effects of these cytokines on the surface molecule expression in HCMCs. Although IL-4 remarkably upregulated lymphocyte function–associated antigen-1, intercellular adhesion molecule-1, and FcϵRI expression and downregulated c-kit expression in HCMCs, IL-13 did not. Conclusions: Our observation that HCMCs produce IL-13 on cross-linking of FcϵRI, which was enhanced by IL-4 priming, supports an important role of mast cells in amplification of allergic reaction and further suggests one of the mechanisms enhancing mast cell function in the microenvironment. (J Allergy Clin Immunol 1998;102:491-502.)