Zinc improves the development of human CD34 + cell progenitors towards Natural Killer cells and induces the expression of GATA-3 transcription factor

• Published in: The international journal of biochemistry & cell biology 2007, Vol.39 (5), p.955-965
• Main Authors: Muzzioli, Mario, Stecconi, Rosalia, Donnini, Alessia, Re, Francesca, Provinciali, Mauro
• Format: Article
• Language: English
• Subjects: Adult; Antigens, CD34 - metabolism; CD34 cell progenitors; CD56 Antigen - metabolism; Cell Differentiation - drug effects; Cell Proliferation - drug effects; Cells, Cultured; Cytotoxicity, Immunologic; Dose-Response Relationship, Drug; GATA-3; GATA3 Transcription Factor - genetics; Gene Expression - drug effects; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - metabolism; Human; Humans; Interleukin-15 - pharmacology; Interleukin-7 - pharmacology; Killer Cells, Natural - cytology; Killer Cells, Natural - drug effects; Killer Cells, Natural - metabolism; Male; Membrane Glycoproteins - metabolism; Membrane Proteins - pharmacology; Middle Aged; Natural Killer cells; NK Cell Lectin-Like Receptor Subfamily D - metabolism; Perforin; Pore Forming Cytotoxic Proteins - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Zinc; Zinc - pharmacology
• ISSN: 1357-2725; 1878-5875
• DOI: 10.1016/j.biocel.2007.01.011

The Natural Killer cell maturation from CD34 + hematopoietic cell precursors is a complex process that requires the synergistic effect of different cytokines and growth factors. Although there have been a number of important advances in our understanding of the Natural Killer differentiation, the developmental step leading to mature Natural Killer cells is still poorly defined. We evaluated the effect of two zinc concentrations (10 and 20 μM) on the kinetic of development of CD34 + cell progenitors towards Natural Killer cells. CD34 + cells were purified from peripheral blood and cultured in medium supplemented with interleukin-15, interleukin-7, Flt 3 ligand, and stem cell factor. CD34 + cells underwent proliferation and progressively lost CD34 antigen and acquired a CD56 + phenotype. These CD56 + cells exerted cytotoxic activity and expressed the CD94 inhibitory receptor. The supplementation with zinc greatly increased both the number of cells in culture and the absolute number of CD56 + cells. Zinc induced higher levels of cytotoxic activity and a higher number of perforin-producing and of CD94-bearing CD56 + cells in comparison with zinc unsupplemented cultures in early stages of Natural Killer cell development. The zinc-induced changes in CD34-derived CD56 + cells were associated with an increased expression of GATA-3, a zinc-finger transcription factor providing for maturation and activity of T and Natural Killer cells. The increase was related to a higher CD56 + cell number (10 μM zinc), or to an increased GATA-3 mRNA transcription in CD56 + cells (20 μM zinc). Our data demonstrate that zinc influences the proliferation and differentiation of CD34 + progenitors.