Characterization of mononuclear blood cell-derived differentiation inducing factors for the human promyelocytic leukemia cell line HL-60.

A search was made for physiologically produced differentiation inducing factor(s) (DIF) for the human promyelocytic leukemia cell line HL-60. Mononuclear blood cells, when stimulated with various mitogens, produced DIF, which induced differentiation of HL-60 into phagocytizing nitro blue tetrazolium reducing cells with the morphologic characteristic of granulopoietic or myelomonocytic cells. Induction of differentiation occurred equally well in serum-containing and serum-free media. Protein synthesis was necessary for elaboration of DIF, which seems to be of a protein nature inasmuch as it is destroyed by proteases. Gel chromatography showed that one or two species of DIF with apparent molecular weights of 40,000 and 25,000 were produced, depending on the type of mitogen used. At least the 40,000-molecular weight DIF was distinct from the colony stimulating activity (CSA), which was produced simultaneously. Our results suggested a role of lymphocytes and/or monocytes for modulation of myelomonocytic hematopoiesis not mediated by CSA. The physiologic importance remains, however, to be demonstrated.