All-Trans Retinoic Acid Directly Inhibits Granulocyte Colony-Stimulating Factor-Induced Proliferation of CD34+ Human Hematopoietic Progenitor Cells

• Published in: Blood 1994-11, Vol.84 (9), p.2940-2945
• Main Authors: Smeland, Erlend B., Rusten, Leiv, Jacobsen, Sten E.W., Skrede, Bj⊘rn, Blomhoff, Rune, Wang, Meng Yu, Funderud, Steinar, Kvalheim, Gunnar, Blomhoff, Heidi Kiil
• Format: Article
• Language: English
• Subjects: Adult; Antigens, CD - analysis; Antigens, CD34; Cell Differentiation - drug effects; Cell Division - drug effects; Colony-Forming Units Assay; Granulocyte Colony-Stimulating Factor - antagonists & inhibitors; Hematopoiesis - drug effects; Hematopoietic Stem Cells - drug effects; Humans; In Vitro Techniques; Tretinoin - pharmacology; Vitamin A - pharmacology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V84.9.2940.2940

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 μmol/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 μmol/L) and chylomicron remnant retinyl esters (0.1 μmol/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 μmol/ 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.