REGULATION OF THE DENSITY OF THE STEM-CELL FACTOR-RECEPTOR (C-KIT) BYTUMOR-NECROSIS-FACTOR-ALPHA ON A HUMAN MYELOID CELL-LINE

The GM/SO cell line bears a high level of stem cell factor receptors ( SCF-R) i. e. c-kit protein, and therefore constitutes a potential mode l for studying the regulation of this crucial receptor on myeloid cell s. In this study we evaluated the effect of tumor necrosis factor alph a (TNF-alpha) on the expression of SCF-R by flow cytometry. In contras t to 1 hour of preincubation, the experiments carried out after 24 hou rs preincubation revealed that TNF-alpha, if added alone, reduced the density of SCF-R on GM/SO cells in a dose-dependent manner. However, i f combined with GM-CSF, which per se downregulates the SCF-R on these cells as well, TNF-alpha antagonized the effect of GM-CSF and slightly increased the density of SCF-R. Yet the cells incubated for 24 hours in medium without cytokines invariably expressed a higher level of SCF -R than the cells incubated in the presence of TNF-alpha and GM-CSF, e ither alone or in combination. In contrast to these cytokines, stem ce ll factor (SCF), which was also tested simultaneously in all experimen ts, downregulated its own natural receptor on these cells also after a preincubation of 1 hour. Furthermore, prolonged exposure of GM/SO cel ls to TNF-alpha for 5-7 days yielded a monocyte-macrophage-like morpho logy of some cells as these cells displayed an apparent glass and plas tic adherence. In contrast, no such morphological changes could be obs erved in the presence of GM-CSF or SCF.