Induction of the high-affinity IgE receptor (FcεRI) on human mast cells by IL-4

Abstract

The high-affinity IgE receptor (FcεRI) is necessary for the induction of IgE-mediated allergic reactions. Cross-linking of FcεRI expressed on mast cells causes the release of various inflammatory mediators, which trigger allergic reactions. Recently, mast cells lacking FcεRI have been observed in vivo and in vitro, suggesting the presence of regulational mechanisms in the induction of FcεRI. In this report, we demonstrate that IL-4 up-regulates FcεRI in cultured human mast cells, which are grown from cord blood mononuclear cells in the presence of stem cell factor and IL-6, and usually lack FcεRI expression. At the protein level, the induction of FcεRI was observed by flow cytometric analysis and the induced FcεRI expression was stable for at least 23 days in the presence of IL-4. Consistently, Northern blot analysis demonstrated the increase of α chain mRNA of FcεRI and revealed that the up-regulation of FcεRI occurred at the transcriptional level. FcεRI induced by IL-4 was functional and caused histamine and β-hexosaminidase release from mast cells upon cross-linking. Taken together, these results indicate a new role of IL-4 in allergic reactions, besides the stimulation of IgE production.