INTERFERON-ALPHA-INDUCED APOPTOSIS IN HUMAN ERYTHROID PROGENITORS

Recombinant human interferon-alpha (rIFN-alpha) inhibits erythropoiesi s, in vivo and in vitro. In an attempt to clarify mechanisms related t o this inhibition, effects of rIFN-alpha on highly purified human peri pheral blood burst-forming units-erythroid (BFU-E) (20-60% purity) wer e 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 interle ukin-3 (rIL-3) was inhibited by rIFN-alpha in a dose-dependent manner, and a significant inhibition occurred at 2000 U/mL rIFN-alpha. Limiti ng dilution analysis demonstrated that rIFN-alpha directly inhibits BF U-E. rIFN-alpha inhibited the proliferative capacity or the colony exp ression of erythroid progenitors, with no relation to the stage of dev elopment, but inhibition of differentiation was not apparent. This evi dence suggested that apoptosis of erythroid progenitors was induced by IFN-alpha. When day-7 cells were incubated with IFN-alpha in the pres ence of rEpo, there was an increased breakdown of total cellular DNA i nto DNA fragments of less than 5 kb; hence, the inhibitory effect of I FN-alpha on erythroid progenitors may mediate apoptosis.