GM-CSF downmodulates c-kit, Fc epsilon RI alpha and GM-CSF receptor expression as well as histamine and tryptase levels in cultured human mast cells

GM-CSF is known primarily as a hematopoietic growth factor, but it has also been shown to inhibit mast cell differentiation in vitro. In order elucida te the mechanisms involved, we investigated the effects of GM-CSF in vitro on the differentiation of human leukemic mast cells (HMC-1 cells) and norma l cord blood-derived mast cells (CBMC) under the influence of SCF, NGF, and fibroblast supernatant (FS). Under all culture conditions, GM-CSF induced a dose-and time-dependent reduction in intracellular histamine levels, tryp tase activity, and numbers of cells immunoreactive for c-Kit and Fc epsilon RI alpha, This effect leveled off between 10-100 ng/ml and after 4 days of culture. There was an associated decrease in mRNA expression for c-kit, Fc epsilon RI alpha and tryptase, In contrast, no significant changes in the expression of the NGF receptor TrkA were noted under the same conditions. T he GMCSF receptor was found in HMC-1 cells and CBMC at both the mRNA and pr otein levels, but its expression decreased during culture with FS, and even more markedly during culture with GM-CSF, GM-CSF thus selectively inhibits in vitro induction and/or upregulation of all major mast cell characterist ics in HMC-1 cells and CBMC irrespective of the growth factors present, and a concomitant downregulation of GM-CSF receptors can counteract these effe cts. GM-CSF may therefore function as a regulatory factor in mast cell grow th and differentiation under normal and pathological conditions.