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. 2009 Feb;15(2):151-8.
doi: 10.1038/nm.1913. Epub 2009 Feb 1.

NAMPT is essential for the G-CSF-induced myeloid differentiation via a NAD(+)-sirtuin-1-dependent pathway

Julia Skokowa  1 , Dan Lan, Basant Kumar Thakur, Fei Wang, Kshama Gupta, Gunnar Cario, Annette Müller Brechlin, Axel Schambach, Lars Hinrichsen, Gustav Meyer, Matthias Gaestel, Martin Stanulla, Qiang Tong, Karl Welte
Affiliations

NAMPT is essential for the G-CSF-induced myeloid differentiation via a NAD(+)-sirtuin-1-dependent pathway

Julia Skokowa et al. Nat Med. 2009 Feb.

Abstract

We identified nicotinamide phosphoribosyltransferase (NAMPT), also known as pre-B cell colony enhancing factor (PBEF), as an essential enzyme mediating granulocyte colony-stimulating factor (G-CSF)-triggered granulopoiesis in healthy individuals and in individuals with severe congenital neutropenia. Intracellular NAMPT and NAD(+) amounts in myeloid cells, as well as plasma NAMPT and NAD(+) levels, were increased by G-CSF treatment of both healthy volunteers and individuals with congenital neutropenia. NAMPT administered both extracellularly and intracellularly induced granulocytic differentiation of CD34(+) hematopoietic progenitor cells and of the promyelocytic leukemia cell line HL-60. Treatment of healthy individuals with high doses of vitamin B3 (nicotinamide), a substrate of NAMPT, induced neutrophilic granulocyte differentiation. The molecular events triggered by NAMPT include NAD(+)-dependent sirtuin-1 activation, subsequent induction of CCAAT/enhancer binding protein-alpha and CCAAT/enhancer binding protein-beta, and, ultimately, upregulation of G-CSF synthesis and G-CSF receptor expression. G-CSF, in turn, further increases NAMPT levels. These results reveal a decisive role of the NAD(+) metabolic pathway in G-CSF-triggered myelopoiesis.

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Comment in

  • Vitamin B3 boosts neutrophil counts.
    Khanna-Gupta A, Berliner N. Khanna-Gupta A, et al. Nat Med. 2009 Feb;15(2):139-41. doi: 10.1038/nm0209-139. Nat Med. 2009. PMID: 19197286 No abstract available.
  • Nicotinamide and neutrophilia.
    Hoffer A. Hoffer A. Nat Med. 2010 Jan;16(1):23; author reply 23. doi: 10.1038/nm0110-23a. Nat Med. 2010. PMID: 20057415 No abstract available.

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