Upregulation of lineage specific receptors and ligands in multipotential progenitor cells is part of an endogenous program of differentiation.
Multipotent hematopoietic progenitor cell lines (FDCP-Mix) infected with a retroviral vector expressing the GM-CSF gene show functional downregulation of the GM-CSF receptor when maintained in IL-3 and activation of the receptor resulting in synchronous differentiation into mature granulocytes and macrophages on withdrawal of IL-3. This system has now been used to investigate whether or not receptors for some of the other growth factors are also influenced as a consequence of differentiation. We show here the lineage specific receptors for M-CSF, G-CSF and erythropoietin are all upregulated, regardless of whether or not differentiation is induced by GM-CSF or by other conditions. Concomitant induction of the mRNA coding for the ligands M-CSF and G-CSF, but not for erythropoietin, suggests that M-CSF and possibly G-CSF facilitate macrophage or granulocyte differentiation by an autocrine stimulation of the lineage specific receptors. FDCP-Mix mutants that are blocked in their ability to differentiate on exposure to GM-CSF, but that still require GM-CSF for proliferation, do not express increased levels of M-CSF receptor nor M-CSF. Based on these data, we suggest that expression of these lineage specific receptors is part of the intrinsic endogenous program of myeloid differentiation.
Just
U
U
Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie, Universität Hamburg, Federal Republic of Germany.
Friel
J
J
Heberlein
C
C
Tamura
T
T
Baccarini
M
M
Tessmer
U
U
Klingler
K
K
Ostertag
W
W
D000818:Animals; D001854:Bone Marrow Cells; D016207:Cytokines / Q000378:metabolism*; D004921:Erythropoietin / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D008024:Ligands; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D009154:Mutation; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D016207:Cytokines; D008024:Ligands; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor