Nitric oxide depletion alters hematopoietic stem cell commitment toward immunogenic dendritic cells

Roberto Tiribuzi, Lucia Crispoltoni, Francesco Tartacca, Antonio Orlacchio, Sabata Martino, Carlo Alberto Palmerini, Aldo Orlacchio

Research output: Contribution to journalArticle

Abstract

Background: NO is a key molecule involved in the regulation of cell survival, proliferation and differentiation in many cell types. In this study we investigated the contribution of NO during the differentiation of human peripheral blood hemopoietic stem cells (CD34+HSCs) toward immunogenic dendritic cells (i-DCs). Methods: We depleted autocrine NO production, using NG-monomethyl-l-arginine monoacetate (l-NMMA) and paracrine NO, using oxy-hemoglobin (HbO2) as a NO scavenger during in vitro differentiation of CD34+HSCs to i-DCs. We monitored the NO level, cell proliferation, phenotype and differentiation potential. Results: We found that the depletion of paracrine or autocrine NO correlated with (I) an active proliferation state at the end of differentiation, when control cells were not proliferating; (II) a significant reduction in the expression levels of differentiative markers (CD1a and HLA-DR) with a parallel high expression of the CD34 marker (III) with a retrieved clonogenic ability compared to control cells. Conclusions: On the whole, our data indicate that the depletion of NO during the commitment stage blocks CD34+HSC differentiation into i-DCs and maintains an undifferentiated, highly proliferating cell population, indicating/revealing a novel role for NO in the commitment of CD34 +HSCs into i-DCs. General significance: The essential finding of the present study is that NO, produced in HSCs by NOS enzymes, may act as autocrine and paracrine effectors regulating the in vitro differentiation process of CD34+-HSCs toward i-DCs.

Original languageEnglish
Pages (from-to)2830-2838
Number of pages9
JournalBBA - General Subjects
Volume1830
Issue number3
DOIs
Publication statusPublished - Mar 2013

Keywords

  • CD34 + hemopoietic stem cell
  • Hemoglobin
  • Lysosomal enzyme
  • N-monomethyl-l-arginine monoacetate
  • Nitric oxide

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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  • Cite this

    Tiribuzi, R., Crispoltoni, L., Tartacca, F., Orlacchio, A., Martino, S., Palmerini, C. A., & Orlacchio, A. (2013). Nitric oxide depletion alters hematopoietic stem cell commitment toward immunogenic dendritic cells. BBA - General Subjects, 1830(3), 2830-2838. https://doi.org/10.1016/j.bbagen.2012.10.019