ALL-TRANS-RETINOIC ACID DIRECTLY INHIBITS GRANULOCYTE-COLONY-STIMULATING FACTOR-INDUCED PROLIFERATION OF CD34(+) HUMAN HEMATOPOIETIC PROGENITOR CELLS

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 mu mol/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 mu mol/L) and chylomicron remnant retinyl esters (0.1 mu mol/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 mu mol/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. (C) 1994 by The American Society of Hematology.