PHORBOL-MYRISTATE ACETATE TREATMENT OF NORMAL HUMAN MYELOID BLAST CELLS PROMOTES MONOPOIESIS AND INHIBITS GRANULOPOIESIS

Fractionation of mononuclear cells from human fetal liver provides a cell population at early stages of myeloid differentiation which, when cultured, generates neutrophils and macrophages for up to a month. These studies describe the further purification of an undifferentiated myeloid blast cell population by rosette sedimentation of unwanted cells, after coating these cells with monoclonal antibodies which identify macrophages and erythroblasts. In culture, the purified blast cells generated only neutrophils and macrophages. When treated with 10 nM PMA, 62% of the purified cells were induced to differentiate towards macrophages within 48 h. PMA-induced cells acquired morphological features of macrophages and synthesized alpha-naphthyl acetate esterase. The differentiation of the remaining blast cells towards neutrophils, seen in untreated cultures, was completely inhibited by PMA, as revealed by the absence of increases in the numbers of cells expressing lactoferrin and an antigen which appears at the promyelocyte stage of differentiation. Thus, PMA effects intracellular changes which both promote monopoiesis and inhibit granulopoiesis, suggesting a reciprocal interaction between intracellular processes which regulate the capacity for the two pathways of maturation. The purified blast cell population provides a good model system for studies of molecular events which regulate the expression of macrophage characteristics.