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(Journal of Leukocyte Biology. 2002;71:641-651.)
© 2002 by Society for Leukocyte Biology

Physiological levels of 1, 25 dihydroxyvitamin D3 induce the monocytic commitment of CD34+ hematopoietic progenitors

Alexis Grande^*, Monica Montanari^*, Enrico Tagliafico^*, Rossella Manfredini^*, Tommaso Zanocco Marani^*, Michela Siena^*, Elena Tenedini^*, Andrea Gallinelli and Sergio Ferrari^*

^* Dipartimento di Scienze Biomediche, Sezione di Chimica Biologica, and
Dipartimento di Scienze Ginecologiche, Ostetriche e Pediatriche, Università di Modena e Reggio Emilia, Modena, Italy

Correspondence: Sergio Ferrari, Dipartimento di Scienze Biomediche, Sezione di Chimica Biologica, Università di Modena e Reggio Emilia, Via Campi 287, 41100, Modena, Italy. E-mail: sergio{at}unimo.it

Although supraphysiological levels of 1, 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.

Key Words: vitamin D3 • hematopoietic stem cells • monocytic differentiation

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