Effects of activin A/erythroid differentiation factor on erythroid and megakaryocytic differentiations of mouse erythroleukemia (Friend) cells: evidence for two distinct modes of cell response.

To further characterize activin A/erythroid differentiation factor (EDF) action on hematopoietic cell differentiation, we examined the effects of activin A/EDF on megakaryocytic and erythroid differentiation by determining acetylcholinesterase (AchE) activity and hemoglobin production in the mouse erythroleukemia (MEL) cell line F55. Activin A/EDF induced AchE activity of F55 cells in a dose-dependent manner. Erythroid differentiation of F55 cells, which was characterized by an increase in dianisidine-positive cells, was also induced by activin A/EDF. The effect of activin A/EDF on hemoglobin synthesis appeared more slowly compared with the effect on AchE activity. Erythroid differentiation induced by activin A/EDF was affected by the initial cell density, but AchE activity was not. Sodium orthovanadate, a tyrosine phosphatase inhibitor, markedly inhibited activin A/EDF-induced erythroid differentiation but not activin A/EDF-induced AchE activity. Other erythroid differentiation inducers, sodium butyrate and butyrylcholine chloride, mildly increased AchE activity in F55 cells, but N,N'-hexamethylene-bis-acetamide (HMBA), dimethyl sulfoxide (DMSO), and genistein did not. Dexamethasone inhibited HMBA-induced erythroid differentiation but did not affect activin A/EDF or sodium butyrate action. These results suggest that F55 cells potentially can differentiate into cells of a megakaryocytic lineage in addition to an erythroid lineage, and that activin A/EDF further potentiates the cell differentiation of this cell line. In addition, our results suggest that the mode of activin A/EDF effects on megakaryocytic differentiation is distinct from that on erythroid differentiation.