title: All-trans retinoic acid directly inhibits granulocyte colony-stimulating factor-induced proliferation of CD34+ human hematopoietic progenitor cells.
abstract: 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.
authors.affiliation: Department of Immunology, Norwegian Radium Hospital, Oslo.
authors.forename: E B
authors.initials: EB
authors.lastname: Smeland
authors.forename: L
authors.initials: L
authors.lastname: Rusten
authors.forename: S E
authors.initials: SE
authors.lastname: Jacobsen
authors.forename: B
authors.initials: B
authors.lastname: Skrede
authors.forename: R
authors.initials: R
authors.lastname: Blomhoff
authors.forename: M Y
authors.initials: MY
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Funderud
authors.forename: G
authors.initials: G
authors.lastname: Kvalheim
authors.forename: H K
authors.initials: HK
authors.lastname: Blomhoff
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003114:Colony-Forming Units Assay; D016179:Granulocyte Colony-Stimulating Factor / Q000037:antagonists & inhibitors*; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D014212:Tretinoin / Q000494:pharmacology*; D014801:Vitamin A / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D014801:Vitamin A; D016179:Granulocyte Colony-Stimulating Factor; D014212:Tretinoin