Granulocytic colony-stimulating factor (G-CSF) does not induce differentiation of WEHI3B(D+) cells but is required for the survival of the mature progeny.

It has been reported previously that cells of the murine myelomonocytic leukaemia cell line WEHI3B(D+) can be induced to differentiate into mature monocytes by incubation with post-endotoxin serum (ES), granulocyte-colony-stimulating factor (G-CSF) or actinomycin D (AMD). We have investigated the kinetics of the differentiation process in suspension cultures, using growth curves and morphological markers to analyze proliferation and differentiation. At low cell densities (less than 10(5)/ml) neither ES nor G-CSF changed the rate of WEHI3B(D+) proliferation; nor did these reagents induce the differentiation of WEHI3B(D+). In contrast, AMD caused growth arrest and initiated cell maturation, which was followed by cell death. The time course of maturation depended on AMD concentration. The addition of either ES or G-CSF at the time of AMD exposure or at times up to 20 hr after the beginning of AMD exposure resulted in a delay of cell death for up to 3 days and in an accumulation of mature monocytes. The kinetics of AMD-induced maturation were not affected by the time of ES or G-CSF addition. We concluded that neither ES nor G-CSF induce the differentiation of WEHI3B(D+) cells directly, but that their presence permits the survival of mature cells produced from WEHI3B(D+) as a result of a short-range autocrine-induced differentiation.