Regulation of Mast Cell Cytokine Production

The studies of mast cell cytokine production described above have shown that maximal induction of cytokine synthesis and release usually occurs in response to IgE-dependent activation. In common with many cell types, there is evidence that FccRI on mast cells is coupled to the phospholipase C effector system that controls two distinct signal transduction pathways, one regulated by Ca ions and the other by protein kinase C (PKC). Exocytotic degranulation is associated with an increased cytoplasmic level of Ca ions, and activation of mast cells can be therefore achieved by the use of calcium iono-phores which raise intracellular calcium concentrations through a receptor-independent mechanism. Alternative mast cell stimuli include phorbol-12-myristate-13-acetate (PMA) which activates PKC and induces mediator secretion from basophils and rodent mast cells but not from human mast cells, and concanavalin A (Con A), a lectin which can stimulate mast cells by cross-linking of cell-bound IgE and/or cell surface glycoproteins. 

In addition to triggering with anti-IgE, most studies of murine mast cells have demonstrated that activation with calcium ionophores also results in significant cytokine 

Evidence also exists that transcriptional and post-transcriptional regulation of mast cell cytokine mRNA may differ for individual cytokines. Thus Wodnar-Filipowicz et al. (1989) demonstrated that in a murine mast cell line, induction of IL-3 mRNA with A23187 was controlled primarily at the post-transcriptional level, 

Overall, these results surest that different regulatory mechanisms may exist in mast cells for the transcription of various cytokines. If these findings apply in vim, then stimuli which favour either activation of PKC or mobilization of intracellular calcium may have distinct effects on the subsequent profile of cytokines released, and hence the type of inflammatory response. Furthermore if heterogeneity exists amongst mast cells in the cytokines they produce, this would provide further evidence that there are subsets of mast cells with specific effector roles. It must be stressed however that the full relevance of these findings to human mast cells is yet to be determined. 

A recent study by Brunner a al. (1993) has confirmed that mature human basophUs synthesize and release IL-4. For optimal secretion, priming with IL-3 for 18-48 h before activation with anti-IgE was required, although low amounts of IL-4 were occasionally detected following incubation with either IL-3 or anti-IgE alone. No spontaneous IL-4 production was detected, and other cytokines known to enhance basophil mediator release, namely IL-5, GM-CSF and nerve growth factor (NGF), 

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