INTERFERON-GAMMA ENHANCES MEGAKARYOCYTE COLONY-STIMULATING ACTIVITY IN MURINE BONE-MARROW CELLS

We have demonstrated previously that interferon-gamma (IFN-gamma) acce lerates platelet recovery in mice with 5-FU induced-marrow aplasia in vivo, However, the mechanism for the regulation of megakaryocyte devel opment induced by IFN-gamma in bone marrow cells in vivo remains unkno wn, To further study the effects of IFN-gamma on megakaryocyte develop ment, various steps during IFN-gamma-mediated accelerated differentiat ion of the megakaryocytes were investigated in serum-free cultures of murine bone marrow cells in vitro, IFN-gamma markedly induced acetylch oline esterase (AChE) activity, a marker of murine megakaryocytic cell s, accompanied by increased colony formation of the megakaryocyte line age, A prominent increase in megakaryocyte number was observed after I FN-gamma treatment, All of these effects were dependent on the presenc e of IL-3, and, therefore, these results suggest that IFN-gamma acts a s a megakaryocyte potentiator (Meg-POT), However, IFN-gamma did not en hance megakaryocyte maturation with respect to increase in cell size, The effects of IFN-gamma on megakaryocyte maturation were similar to t hose observed after treatment with higher doses of IL-3 alone, Meg-POT is defined as a factor that induces megakaryocyte maturation, Since I FN-gamma enhanced IL-3-dependent megakaryocyte colony formation and pr oliferation rather than megakaryocyte maturation, the effects on megak aryocyte 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-st imulating factor activity, The effect of IFN-gamma in vitro appears to correlate well with the acceleration of platelet recovery in vivo.