Interferon-gamma enhances megakaryocyte colony-stimulating activity in murine bone marrow cells

We have demonstrated previously that interferon-gamma (IFN-gamma) accelerates platelet recovery in mice with 5-FU induced-marrow aplasia in vivo, However, the mechanism for the regulation of megakaryocyte development induced by IFN-gamma in bone marrow cells in vivo remains unknown, To further study the effects of IFN-gamma on megakaryocyte development, various steps during IFN-gamma-mediated accelerated differentiation of the megakaryocytes were investigated in serum-free cultures of murine bone marrow cells in vitro, IFN-gamma markedly induced acetylcholine esterase (AChE) activity, a marker of murine megakaryocytic cells, accompanied by increased colony formation of the megakaryocyte lineage, A prominent increase in megakaryocyte number was observed after IFN-gamma treatment, All of these effects were dependent on the presence of IL-3, and, therefore, these results suggest that IFN-gamma acts as a megakaryocyte potentiator (Meg-POT), However, IFN-gamma did not enhance megakaryocyte maturation with respect to increase in cell size, The effects of IFN-gamma on megakaryocyte maturation were similar to those observed after treatment with higher doses of IL-3 alone, Meg-POT is defined as a factor that induces megakaryocyte maturation, Since IFN-gamma enhanced IL-3-dependent megakaryocyte colony formation and proliferation rather than megakaryocyte maturation, the effects on megakaryocyte development, which were induced by IFN-gamma treatment, seem to be different from the effects of a Meg-POT, We, therefore, propose a new function for IFN-gamma as an enhancer of megakaryocyte colony-stimulating factor activity, The effect of IFN-gamma in vitro appears to correlate well with the acceleration of platelet recovery in vivo.