HUMAN MAST-CELLS PRODUCE IL-13 BY HIGH-AFFINITY IGE RECEPTOR CROSS-LINKING - ENHANCED IL-13 PRODUCTION BY IL-4-PRIMED HUMAN MAST-CELLS

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 t he 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 v ariety of cytokines in cord blood-derived human cultured mast cells (H CMCs) 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 importa nt roles in allergic diseases, we examined protein as well as mRNA exp ression of both cytokines in HCMCs. Results: HCMCs did not express eit her 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 cy toplasm, although IL-4 secreted in the supernatant was below detectabl e levels in contrast to a significant amount of IL-13, Stimulation of HCMCs by cross-linking of the high-affinity IgE receptor (Fc epsilon R I) induced the expression of IL-13 mRNA and protein, but not IL-4, Alt hough we previously found that IL-4 upregulates Fc epsilon RI expressi on on HCMCs, when HCMCs were first cultured in the presence of IL-4 an d then activated through Fc epsilon RI cross-linking, remarkable incre ase was found in IL-13 production. Furthermore, although IL-4 was stil l undetectable at protein level, IL-4 mRNA expression was induced in t he IL-4-primed HCMCs stimulating Fc epsilon RI cross-linking. In addit ion, we examined the effects of these cytokines on the surface molecul e expression in HCMCs. Although IL-4 remarkably upregulated lymphocyte function-associated antigen-1, intercellular adhesion molecule-1, and Fc epsilon RI expression and downregulated c-kit expression in HCMCs, IL-13 did not. Conclusions: Our observation that HCMCs produce IL-13 on cross-linking of Fc epsilon RI, 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 ce ll function in the microenvironment.