Primitive human hematopoietic progenitor cells express receptors for granulocyte-macrophage colony-stimulating factor

Most cytokines act only synergistically in assays of primitive progenitor cell proliferation, and effects have usually been observed first after prolonged cell culture. Studies reporting that primitive progenitors lack receptors for a number of cytokines, including granulocyte-macrophage colony stimulating factor (GM-CSF), could indicate that several "synergistic" cytokines primarily affect cells that have differentiated in vitro. Here, however, we show that freshly isolated primitive progenitor cells (CD34hi CD38-) express receptors for GM-CSF at levels 20%-30% of granulo-monocytic progenitors. Although GM-CSF had minimal effects on the survival or proliferation of primitive progenitors when added alone, the cytokine enhanced stem cell factor (SCF) induced cell cycle entry in the first generation. The effect was not observed when cells were incubated sequentially with SCF and GM-CSF. The results suggest that the synergistic effects of GM-CSF are mediated directly on primitive progenitor cells and that the cytokine may be useful to enhance cell cycle entry of hematopoietic stem cells.