U. Just et al., UP-REGULATION OF LINEAGE-SPECIFIC RECEPTORS AND LIGANDS IN MULTIPOTENTIAL PROGENITOR CELLS IS PART OF AN ENDOGENOUS PROGRAM OF DIFFERENTIATION, Growth factors, 9(4), 1993, pp. 291-300
Multipotent hematopoietic progenitor cell lines (FDCP-Mix) infected wi
th a retroviral vector expressing the GM-CSF gene show functional down
regulation of the GM-CSF receptor when maintained in IL-3 and activati
on of the receptor resulting in synchronous differentiation into matur
e 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 different
iation. We show here the lineage specific receptors for M-CSF, G-CSF a
nd erythropoietin are all upregulated, regardless of whether or not di
fferentiation 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 stil
l require GM-CSF for proliferation, do not express increased levels of
M-CSF receptor nor M-CSF. Based on these data, we suggest that expres
sion of these lineage specific receptors is part of the intrinsic endo
genous program of myeloid differentiation.