Action of human interleukin-4 and stem cell factor on erythroid and mixed colony formation by peripheral blood-derived CD34+ c-kit(high) or CD34+ c-kit(low) cells.
We studied the interaction of interleukin (IL)-4 and other burst-promoting activity (BPA) factors, such as IL-3, granulocyte/macrophage colony-stimulating factor (GM-CSF), IL-9 and stem cell factor (SCF), on erythroid burst-forming unit (BFU-E) and erythrocyte-containing mixed (CFU-Mix) colony formation in serum-free culture. IL-4 alone did not support mixed colony formation in the presence of erythropoietin (Epo). However, IL-4 showed weak but significant BPA when peripheral blood (PB)-derived CD34+c-kit(low) cells were used as the target population. The BPA of IL-4 was much weaker than that of IL-3, which exerted the most potent activity, as previously reported. When CD34+c-kit(high) cells were used as the target, four factors known to have BPA, IL-3, GM-CSF, IL-9 and SCF, could express BPA. In contrast, IL-4, alone failed to support erythroid burst formation. Interestingly, IL-4 showed a remarkable enhancing effect with SCF in promoting the development of erythroid burst and erythrocyte-containing mixed colonies from CD34+c-kit(low) and CD34+c-kit(high) cells. Delayed addition of SCF+Epo or IL-4+Epo to the cultures initiated with either IL-4 or SCF alone clearly demonstrated that SCF was a survival factor for both BFU-E and CFU-Mix progenitors. In contrast, the survival effect of IL-4 was much weaker than that of SCF, and appeared to be more important for progenitors derived from CD34+c-kit(low) cells than for those derived from CD34+c-kit(high) cells. It was recently reported that CD34+c-kit(low) cells represent a more primitive population than CD34+c-kit(high) cells. Taken together, these results suggest that IL-4 helps to recruit primitive progenitor cells in the presence of SCF.
Sonoda
Y
Y
Department of Hygiene, Kyoto Prefectural University of Medicine, Japan.
Kimura
T
T
Ohmizono
Y
Y
Sakabe
H
H
Tanimukai
S
S
Yokota
S
S
Clark
S C
SC
Abe
T
T
D018952:Antigens, CD34; D015672:Erythroid Precursor Cells / Q000166:cytology*; D004921:Erythropoietin / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D016906:Interleukin-9 / Q000494:pharmacology; D019089:Stem Cell Factor / Q000494:pharmacology*
D018952:Antigens, CD34; D007377:Interleukin-3; D016906:Interleukin-9; D019089:Stem Cell Factor; D004921:Erythropoietin; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor