Stem Cells, Vol 12, 514-520, Copyright © 1994 by AlphaMed Press
Synergy among erythropoietin, interleukin 3, stem cell factor (c-kit ligand) and interferon-gamma on early human hematopoiesis
Y Kawano, Y Takaue, A Hirao, J Sato, T Abe, T Suzue, S Saito, Y Okamoto and Y Kuroda
Department of Pediatrics, University of Tokushima, Japan.
The stimulatory effect of interferon-gamma (IFN-gamma) on human early
hematopoiesis was investigated using CD34+ cells that were purified from
peripheral blood as a target. In the presence of human interleukin 3 (IL-3)
and stem cell factor (SCF), the growth of colony forming units for
granulocyte/macrophage (CFU-GM) in serum-free methylcellulose culture was
enhanced up to 5.5-fold over baseline colony formation (n = 10, mean +/-
SE, 3.18 +/- 1.00) by coculture with 2.5 x 10(3) U/ml IFN- gamma, whereas
burst forming units-erythroid (BFU-E) growth induced by additional
erythropoietin (Epo) was reduced dose-dependently. Liquid- suspension
culture of the target cells for 24 h with IFN-gamma before secondary
plating in serum-free methylcellulose resulted in a marked increase in the
colony numbers; 3.62 +/- 1.04-fold for CFU-GM and 5.72 +/- 2.32-fold for
BFU-E (n = 5). The effect was most striking in the growth of erythroid
lineage supported by Epo alone in serum-free culture. Delayed addition of
IFN-gamma between days 4 and 7 of methylcellulose culture suppressed CFU-GM
growth, but not that of BFU- E. These results suggest that IFN-gamma is an
essential cytokine that affects human hematopoiesis and exerts a bimodal
effect on stem cell maturation; potentiating or replacing the effect of
early-acting cytokines such as SCF or IL-3, and suppressing the growth of
matured progenitor cells.
