IL-4 enhances proliferation and mediator release in mature human mast cells

Tissue mast cells (MC) are recognized as key effector cells of immediate-ty pe allergic reactions releasing inflammatory mediators and cytokines on sti mulation with antigen, but they also might be involved in IgE-independent i nflammatory and tissue repair processes. The mechanism of human MC regulati on in tissue is not fully understood. Here, we show that IL-4. in synergy w ith stem cell factor (SCF), regulates the function of purified human MC iso lated from intestinal tissue. Whereas SCF induced only marginal proliferati on of MC cultured in vitro up to 4 weeks, addition of IL-4 and SCF strongly increased the proliferation rate. Moreover, IL-4, which by itself had no v isible effect on human MC, enhanced the release of histamine, leukotriene C -4, and IL-5 in MC triggered by IgE receptor crosslinking. The IL-4 effects occurred In a dose-dependent fashion (ED50 = 100 pg/ml) and could be total ly blocked by a competitive IL-4 receptor antagonist. Our data indicate tha t IL-4 is an important regulator of human MC function and suggest that matu re MC retain the capacity to proliferate in a particular tissue environment .