STEM-CELL FACTOR CAN OVERCOME INHIBITION OF HIGHLY PURIFIED HUMAN BURST-FORMING UNITS-ERYTHROID BY INTERFERON-GAMMA

Highly purified human blood burst-forming units-erythroid (BFU-E) were used to study the effects of interferon gamma(lFN gamma). IFN gamma i nhibited erythroid colony formation, cell proliferation, and different iation of day 3 to day 6 mature BFU-E in a dose-dependent manner. The primitive BFU-E (day 1 and day 2 cells) and later day 7 cells were les s affected. IFN gamma dose-response experiments demonstrated that the number and size of erythroid colonies were reduced at a concentration of 500 U/ml with more complete inhibition at 1,000 U/ml. inhibition of day 4 to day 6 erythroid progenitors was first noted by 72 h of incub ation with IFN gamma, and target cell growth and differentiation conti nued to decrease with further incubation. IFN gamma also induced eryth roblast apoptosis which was demonstrated by both nuclear condensation and fragmentation plus flow cytometry with in situ end-labelling. Beca use day 3 to day 6 cells need stem cell factor (SCF) for development i n serum-free culture, the relationship of IFN gamma inhibition to this growth factor was investigated. The reduction in the number of erythr oid colonies by lFN gamma was reversed by SCF although the colony size was not completely re-established. In contrast, interleukin-3 did not have the capacity to overcome the inhibitory effects of IFN gamma. Si nce IFN gamma blood levels are elevated in some anemias of chronic dis ease, IFN gamma may have a role in promoting this anemia and its inhib itory effect might be better overcome by SCF plus EP. However, the mec hanism by which these growth factors overcome the inhibition of IFN ga mma, or vice versa, is unknown at the present time. (C) 1995 Wiley-lis s, lnc.