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.
Böhmer
R M
RM
Melbourne Tumour Biology Branch, Ludwig Institute for Cancer Research, Australia.
Burgess
A W
AW
D000818:Animals; D002452:Cell Count; D002453:Cell Cycle; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D003609:Dactinomycin / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor; D006098:Granulocytes / Q000378:metabolism*; D007951:Leukemia, Myeloid; D051379:Mice; D014407:Tumor Cells, Cultured
D003115:Colony-Stimulating Factors; D016179:Granulocyte Colony-Stimulating Factor; D003609:Dactinomycin