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 stimulating 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 volunteers. When the cells were cultured in the presence of IFN-gamma, even without 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 the 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 detected 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 cytometric analysis or fluorometric protease assay. IFN-gamma induced Fas expression of the cells without the activation of caspase8 or caspase3 during 16 hours of incubation, while deprivation of EPO induced expression of Fas and the activation of both caspase8 and caspase3. We propose that IFN-gamma produces a stimulating signal for the survival of mature erythroid progenitor cells by reducing apoptosis through a mechanism other than modulating Fas and one related to the expression of Bcl-x. (Blood. 2000;95:3742-3749)
Choi
I
I
Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
Muta
K
K
Wickrema
A
A
Krantz
S B
SB
Nishimura
J
J
Nawata
H
H
D017304:Annexin A5 / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D053938:DNA Fragmentation; D004921:Erythropoietin / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology; D007700:Kinetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor / Q000494:pharmacology
D017304:Annexin A5; D016895:Culture Media, Serum-Free; D007377:Interleukin-3; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D004921:Erythropoietin; D007371:Interferon-gamma; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases