Interferon-alpha-induced apoptosis in human erythroid progenitors.
Recombinant human interferon-alpha (rIFN-alpha) inhibits erythropoiesis, in vivo and in vitro. In an attempt to clarify mechanisms related to this inhibition, effects of rIFN-alpha on highly purified human peripheral blood burst-forming units-erythroid (BFU-E) (20-60% purity) were compared with effects on erythroid progenitors in various stages of development. Day-1 and -7 cultured cells were equivalent to primitive BFU-E and colony-forming units-erythroid (CFU-E), respectively. Day-1 BFU-E supported by recombinant human erythropoietin (rEpo) and interleukin-3 (rIL-3) was inhibited by rIFN-alpha in a dose-dependent manner, and a significant inhibition occurred at 2000 U/mL rIFN-alpha. Limiting dilution analysis demonstrated that rIFN-alpha directly inhibits BFU-E rIFN-alpha inhibited the proliferative capacity or the colony expression of erythroid progenitors, with no relation to the stage of development, but inhibition of differentiation was not apparent. This evidence suggested that apoptosis of erythroid progenitors was induced by IFN-alpha. When day-7 cells were incubated with IFN-alpha in the presence of rEpo, there was an increased breakdown of total cellular DNA into DNA fragments of less than 5 kb; hence, the inhibitory effect of IFN-alpha on erythroid progenitors may mediate apoptosis.
Tarumi
T
T
Department of Internal Medicine II, Hokkaido University School of Department of Internal Medicine II, Hokkaido University School of Medicine, Japan.
Sawada
K
K
Sato
N
N
Kobayashi
S
S
Takano
H
H
Yasukouchi
T
T
Takashashi
T
T
Sekiguchi
S
S
Koike
T
T
D000328:Adult; D017209:Apoptosis; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004905:Erythrocyte Aging; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000502:physiology*; D004920:Erythropoiesis; D004921:Erythropoietin / Q000494:pharmacology; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors
D007370:Interferon Type I; D007377:Interleukin-3; D011994:Recombinant Proteins; D004921:Erythropoietin; D004247:DNA