Differentiation of the IL-3-dependent NFS-60 cell line and adaption to growth in macrophage colony-stimulating factor.
Macrophage CSF (M-CSF) induces responsive bone marrow precursors into rapid growth and differentiation to mature macrophages. Available cell lines that depend on M-CSF for growth are well differentiated and rather adherent. We investigated the effects of M-CSF on immature myeloid cell lines as models of the marrow precursors. The murine line NFS-60 requires IL-3 for growth and also responds to granulocyte-CSF and granulocyte-macrophage-CSF. Cultures of one NFS-60 subline, when switched from IL-3 to 10% L cell conditioned media, a source of M-CSF, or purified M-CSF, frequently acquired large, adherent cells. The adherent cells grew slowly in the presence of M-CSF, in contrast to the majority population of small, round, rapidly growing cells. The large cells had properties of differentiated macrophages that were absent in the nonadherent cells. Cells with macrophage phenotype were not observed in IL-3-supported cultures over many passages. A subline was derived from NFS-60 that grew rapidly and continuously in human or murine M-CSF as round, nonadherent cells. The line, called M-NFS-60, responded well to M-CSF and IL-3, weakly to granulocyte-CSF and not at all to murine granulocyte-macrophage-CSF, IL-4, or human IL-1. A mAb to human M-CSF specifically inhibited only M-NFS-60 proliferation induced by the human growth factor, whether produced by mammalian or bacterial cells. This study shows two effects of M-CSF on the IL-3-dependent NFS-60 line. Upon first exposure to M-CSF, cells may undergo global differentiation to slowly replicating macrophages in conditions we have not been able to define. The more common effect is rapid growth of immature myeloid cells like the bone marrow precursors, but with a block to differentiation. Thus, these cells may be useful as models of M-CSF-induced differentiation, and of permanently maintained macrophage precursors.
Nakoinz
I
I
Department of Cell Biology, Cetus Corporation, Emeryville, CA 94608.
Lee
M T
MT
Weaver
J F
JF
Ralph
P
P
D000222:Adaptation, Physiological; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D003124:Colorimetry; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000032:analysis; D016186:Receptor, Macrophage Colony-Stimulating Factor; D011994:Recombinant Proteins / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D003115:Colony-Stimulating Factors; D007377:Interleukin-3; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor