Stem cell factor and interleukin-4 induce murine bone marrow cells to develop into mast cells with connective tissue type characteristics in vitro

In this study, we have developed a method to obtain mast cells with connect ive tissue type mast cell (CTMC) characteristics directly from mouse bone m arrow (BM) cells, BM cells were grown for 3 weeks in presence of interleuki n-4 (IL-4) plus stem cell factor (SCF), SCF alone poorly supported growth a nd development of mast cells, IL-I dose-dependently enhanced the expression of c-kit and high-affinity receptor for IgE (Fc epsilon RI) on the cell su rface of SCF-cultured BM cells. Furthermore, cytoplasmic granulation and hi stamine synthesis of BM-derived mast cells were increased in presence of IL -4 and SCF, Histochemical staining demonstrated that granules were safranin positive. BM-derived mast cells could he activated for granule exocytosis (beta-hexosaminidase release) and lipid mediator generation (LTC, productio n) via Fc epsilon RI after sensitization with IgE and subsequent crosslinki ng with multivalent antigen. In addition, mast cells derived from BM cells cultured with SCF plus IL-4 could be activated by substance P, a nonimmunol ogic stimulus, to release beta-hexosaminidase. The results presented indica te that IL-4 and SCF both hale a prominent role in the development of mast cells from murine BM cells in vitro.,Mast cells can directly be derived fro m BM cells in presence of SCF and IL-4 and the cultured cells show typical hallmarks of CTMC, indicating that precursor cells for CTMC ma, be present in BM. The described culture procedure may. be useful to investigate the mo lecular aspects of the development of committed mast cell lineages. (C) 199 9 International Society for Published by Elsevier Science Inc. Experimental Hematology.