Blood, Vol. 95 No. 12 (June 15), 2000:
pp. 3742-3749
Interferon gamma delays apoptosis of mature erythroid progenitor
cells in the absence of erythropoietin
Ilseung Choi,
Koichiro Muta,
Amittha Wickrema,
Sanford B. Krantz,
Junji Nishimura, and
Hajime Nawata
From the Department of Medicine and Bioregulatory Science, Graduate
School of Medical Science, Kyushu University, Fukuoka, Japan; Stem
Cell/Bone Marrow Processing Laboratory, Hematology/Oncology Section,
University of Illinois; Department of Medicine-Hematology/Oncology,
Vanderbilt University School of Medicine; and Department of Clinical
Immunology, Medical Institute of Bioregulation, Kyushu University,
Beppu, Japan.
Based on the hypothesis that interferon gamma (IFN-
) may have
stimulating effects on survival of hematopoietic progenitor cells, we
examined the effect of IFN- 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-, 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- reduced the extent of apoptosis of the cells, as
well as EPO. DNA fragmentation of ECFCs was also reduced by IFN-. In
cells cultured with IFN- 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- 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- 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.
