DIFFERENTIAL RELEASE OF MAST-CELL INTERLEUKIN-6 VIA C-KIT

Mast cells represent a potential source of interleukin-6 (IL-6) and ot her cytokines that have been implicated in host defense, tissue mainte nance/remodeling, immunoregulation, and many other biologic responses. In acquired immune responses to parasites or allergens, the extensive IgE-dependent activation of mast cells via Fc,RI can result in the re lease of large quantities of biogenic amines that are stored in the ce lls' cytoplasmic granules as well as the production of lipid mediators and many cytokines; these products together can orchestrate an intens e inflammatory response. We now report that activation of mouse mast c ells via c-kit, the receptor for the pleiotropic survival/growth facto r, stem cell factor (SCF), can induce the release of IL-6. Upon challe nge with SCF, bone marrow-derived cultured mouse mast cells (BMCMCs) r eleased amounts of IL-6 that were greater than 100-fold more than thos e produced by unstimulated cells, but that were substantially less tha n those produced in response to IgE and specific antigen. Moreover, BM CMCs released IL-6 upon challenge with concentrations of SCF that resu lted in little or no detectable release of tumor necrosis factor-alpha leukotriene C-4, histamine, or serotonin, These findings indicate tha t SCF, a widely expressed protein that is critical for mast cell devel opment and survival, can also regulate the differential release of mas t cell mediators. (C) 1997 by The American Society of Hematology.