title: Physiological levels of 1alpha, 25 dihydroxyvitamin D3 induce the monocytic commitment of CD34+ hematopoietic progenitors.
abstract: Although supraphysiological levels of 1alpha, 25 dihydroxyvitamin D3 (VD) have been demonstrated extensively to induce the monomacrophagic differentiation of leukemic myelo- and monoblasts, little is known about the role that physiological levels of this vitamin could play in the regulation of normal hematopoiesis. To clarify this issue, we adopted a liquid-culture model in which cord blood CD34+ hematopoietic progenitors, induced to differentiate in the presence of different combinations of cytokines, were exposed to VD at various concentrations and stimulation modalities. The data obtained show that physiological levels of VD promote a differentiation of CD34+ hematopoietic progenitors characterized by the induction of all the monomacrophagic immunophenotypic and morphological markers. This effect is not only exerted at the terminal maturation but also at the commitment level, as demonstrated by the decrease of highly undifferentiated CD34+CD38- hematopoietic stem cells, the down-regulation of CD34 antigen, and the increase of monocyte-committed progenitors. Molecular analysis suggests that the VD genomic signaling pathway underlies the described differentiation effects.
authors.affiliation: Dipartimento di Scienze Biomediche, Sezione di Chimica Biologica, Università di Modena e Reggio Emilia, Modena, Italy.
authors.forename: Alexis
authors.initials: A
authors.lastname: Grande
authors.forename: Monica
authors.initials: M
authors.lastname: Montanari
authors.forename: Enrico
authors.initials: E
authors.lastname: Tagliafico
authors.forename: Rossella
authors.initials: R
authors.lastname: Manfredini
authors.forename: Tommaso
authors.initials: T
authors.lastname: Zanocco Marani
authors.forename: Michela
authors.initials: M
authors.lastname: Siena
authors.forename: Elena
authors.initials: E
authors.lastname: Tenedini
authors.forename: Andrea
authors.initials: A
authors.lastname: Gallinelli
authors.forename: Sergio
authors.initials: S
authors.lastname: Ferrari
mesh_terms: D018952:Antigens, CD34 / Q000032:analysis*; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology
chemical_list: D018952:Antigens, CD34; D016173:Macrophage Colony-Stimulating Factor; D002117:Calcitriol