Interferon gamma has dual potential in inhibiting or promoting survival and growth of hematopoietic progenitors: interactions with stromal cell-derived factor 1.

We explored the possibility that interferon gamma (IFN-gamma) has bidirectional functions in the survival and growth of hematopoietic progenitors, especially with regard to interactions with stromal cell-derived factor 1 (SDF-1). IFN-gamma partially rescued normal bone marrow CD34+ cells and colony-forming cells from apoptosis induced by serum and hematopoietic growth factor (HGF) deprivation, and SDF-1 further enhanced cell survival. Short-term IFN-gamma treatment of CD34+ cells in the absence of serum and HGFs enhanced the clonal growth of the cells in synergy with SDF-1. In contrast, IFN-gamma inhibited the clonal growth of hematopoietic progenitor cells in a standard methylcellulose clonogenic assay and inhibited the HGF-mediated survival of normal CD34+ cells. The addition of SDF-1 did not alter these outcomes. IFN-gamma did not enhance SDF-1-induced activation of PI3K/Akt or up-regulate the expression of CXCR4 or its function in bone marrow CD34+ cells. IFN-gamma up-regulated Socs1 messenger RNA expression in normal CD34+ cells, which was further enhanced with the addition of HGFs. These results indicate that IFN-gamma, partly in concert with SDF-1, exerts dual effects on the survival and growth of hematopoietic progenitor cells; the effects of IFN-gamma on hematopoietic progenitor cells can differ, depending on the particular in vitro experimental conditions, especially the presence of HGFs.