Open AccessSynergistic suppression: anomalous inhibition of the proliferation of factor-dependent hemopoietic cells by combination of two colony-stimulating factors.
Author(s) -
Donald Metcalf,
Nicos A. Nicola,
Nicholas M. Gough,
Michael J. Elliott,
Grant A. McArthur,
M Li
Publication year - 1992
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.89.7.2819
Subject(s) - macrophage colony stimulating factor , haematopoiesis , biology , granulocyte macrophage colony stimulating factor , granulocyte macrophage colony stimulating factor receptor , growth factor , microbiology and biotechnology , progenitor cell , receptor , colony stimulating factor , macrophage , cell culture , cytokine , tyrosine kinase , stem cell factor , immunology , signal transduction , stem cell , biochemistry , in vitro , genetics
Cells of the continuous murine hemopoietic cell line FDC-P1 expressing macrophage-colony-stimulating factor (M-CSF) receptors following retroviral insertion of murine c-fms cDNA proliferated clonally when stimulated by granulocyte/macrophage (GM)-CSF, multipotential CSF, or M-CSF. However, M-CSF combined with either GM-CSF or multi-CSF, even at low CSF concentrations, strongly inhibited colony formation, with loss of clonogenicity in affected cells accompanied by increased macrophage differentiation. Stimulation by these CSF combinations did not induce short-term changes in CSF receptor expression or internalization. FDC-P1 cells expressing another inserted tyrosine kinase receptor, basic fibroblast growth factor receptor, did not exhibit suppression when GM-CSF was combined with fibroblast growth factor. This phenomenon of synergistic suppression may have relevance for the future clinical use of combinations of CSFs, because a potentially similar suppression is also observable with some normal macrophage progenitor cells.