Changes in cellular ferritin content during myeloid differentiation of human leukemic cell lines

The human promyelocytic cell lines HL-60 can be induced to undergo differentiation to either granulocyte- or macrophage-like cells. We followed the changes in the synthesis and content of ferritin in this and other cell lines during differentiation. Ferritin content of HL-60 cells ranged from 11 to 81 fg/cell, depending on the clone tested. Following exposure to dimethylsulfoxide (DMSO) or retinoic acid (RA) an increase in ferritin and a decrease in total protein synthesis was observed, resulting in increased ferritin content, reaching a peak after 2 days. This increase occurred prior to the appearance of the typical morphological and functional characteristics of mature granulocytes. A correlation was found between concentrations of DMSO effective in inducing differentiation and the increase in ferritin content. Other inducers of granulocyte differentiation had a similar effect, while 12-O-tetradecanoylphorbol-13-acetate (TPA), an inducer of macrophage differentiation, had not. Another human cell line (U-937), which was induced into monocyte-like cells by RA, showed a twofold increase in ferritin content following differentiation. Addition of iron to the culture medium increased ferritin content of both differentiating and non-differentiating cells, but the former responded to lower concentrations of iron. The increase in ferritin during differentiation, however, was not related to an accelerated iron uptake. The present results suggest that changes in the intracellular ferritin of the developing myeloid cells may play a regulating role in the process of maturation of these cells.