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All-trans retinoic acid directly inhibits granulocyte colony- stimulating
factor-induced proliferation of CD34+ human hematopoietic progenitor cells
EB Smeland, L Rusten, SE Jacobsen, B Skrede, R Blomhoff, MY Wang, S Funderud, G Kvalheim and HK Blomhoff
Department of Immunology, Norwegian Radium Hospital, Oslo.
In this study we examine the effects of retinoids on purified CD34+ human
hematopoietic progenitor cells. All-trans retinoic acid inhibited
granulocyte colony-stimulating factor (G-CSF)-induced proliferation of
CD34+ cells in short-term liquid cultures in a dose-dependent fashion with
maximal inhibition of 72% at a concentration of retinoic acid of 1 mumol/L.
Although no significant effects were observed on granulocyte- macrophage
CSF (GM-CSF)--interleukin-3--or stem cell factor (SCF)- induced
proliferation, the combinations of G-CSF and each of these cytokines were
all inhibited. Moreover, retinol (3 mumol/L) and chylomicron remnant
retinyl esters (0.1 mumol/L) in concentrations normally found in human
plasma also had inhibitory effects. Single-cell experiments showed that the
effects of retinoic acid were directly mediated. Retinoids also
significantly inhibited G-CSF-induced colony formation in semisolid medium,
with 88% inhibition observed at a concentration of retinoic acid of 1
mumol/L. However, we did not observe any effects of retinoic acid on
G-CSF-induced differentiation as assessed by morphology and flowcytometry.
Similar to previous findings using total bone marrow mononuclear cells, we
observed a stimulation of GM-CSF-induced colony formation after 14 days. We
also observed a stimulatory effect of low doses of retinoic acid (30
nmol/L) on blast-cell colony formation on stromal cell layers. Taken
together, the data indicate that vitamin A present in human plasma has
inhibitory as well as stimulatory effects on myelopoiesis.
Volume 84,
Issue 9,
pp. 2940-2945,
11/01/1994
Copyright © 1994 by The American Society of Hematology
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