The regulation of mast cell growth and differentiation depends upon the sequential availability of specific growth factors and the expression of their corresponding receptors. Among the various cytokines that promote mast cell growth, the most important is stem cell factor (SCF) which is produced in tissues by stromal cells. We have reported that the decrease in mast cells observed in tissues that follows topical steroid administration is due to the effect of the steroid on SCF production. In an effort to also identify cytokines that inhibit human mast cell growth, we cultured SCF-dependent human bone marrow-derived mast cells (HBMCs) in the presence of interferon (IFN) gamma-1b. In these cultures, HBMCs significantly decreased in number. IFN-gamma-1b was thus able to suppress mast cell growth from CD34-positive cells, suggesting that this agent should be considered as a candidate cytokine for the treatment of disorders of mast cell proliferation.We previously reported that human mast cells arise from CD34-positive human stem cells in SCF (c-kit positive). To further characterize the human mast cell precursor, we sorted CD34-positive cells using a variety of candidate markers. The most promising was CD13. A series of experiments based on cell sorting and colony formation then led to the conclusion that CD34-positive, c-kit-positive, CD13-positive cells gave rise to all mast cells in culture. In additional studies we have also demonstrated that mast cells express connexins which are involved in cell-to-cell communication. Finally, in studies in mast cell deficient mice we found that the Wv c-kit mutant allele remains able to induce a signal, which leads to adhesion. - Mast cells, stem cells, monocytes, cell culture, differentiation, colony formation, stem cell factor, IL3, IFN-gamma - Human Subjects
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