Interferon gamma delays apoptosis of mature erythroid progenitor cells in the absence of erythropoietin

Based on the hypothesis that interferon gamma (IFN-gamma) may have stimulat ing effects on survival of hematopoietic progenitor cells, we examined the effect of IFN-gamma on apoptosis of mature erythroid colony-forming cells ( ECFCs) derived from human peripheral blood obtained from normal, healthy vo lunteers. When the cells were cultured in the presence of IFN-gamma, even w ithout erythropoietin (EPO), the viability of the cells was maintained for at least 36 hours, When apoptosis of ECFCs was assessed by flow cytometric analysis', using annexin V, IFN-gamma reduced the extent of apoptosis of th e cells, as well as EPO, DNA fragmentation of ECFCs was also reduced by IFN -gamma, In cells cultured with IFN-gamma alone, expression of Bcl-x was det ected but the level of expression decreased gradually during incubation for 36 hours, and the expression level was lower than incubation with EPO, Fas expression and activation of downstream caspases were assessed by flow cyt ometric analysis or fluorometric protease assay. IFN-gamma induced Fas expr ession of the cells without the activation of caspase8 or caspase3 during 1 6 hours of incubation, while deprivation of EPO induced expression of Fas a nd the activation of both caspase8 and caspase3, We propose that IFN-gamma produces a stimulating signal for the survival of mature erythroid progenit or cells by reducing apoptosis through a mechanism other than modulating Fa s and one related to the expression of Bcl-x. (C) 2000 by The American Soci ety of Hematology.