title: Interferon gamma selectively inhibits very primitive CD342+CD38- and not more mature CD34+CD38+ human hematopoietic progenitor cells.
abstract: To assess the effects of interferon gamma (IFN-gamma) on very primitive hematopoietic progenitor cells, CD34(2+)CD38- human bone marrow cells were isolated and cultured in a two-stage culture system, consisting of a primary liquid culture phase followed by a secondary semisolid colony assay. CD34(2+)CD38- cells needed at least the presence of interleukin 3 (IL-3) and kit ligand (KL) together with either IL-1, IL-6, or granulocyte-colony-stimulating factor (G-CSF) in the primary liquid phase in order to proliferate and differentiate into secondary colony-forming cells (CFC). Addition of IFN-gamma to the primary liquid cultures inhibited cell proliferation and generation of secondary CFC in a dose-dependent way. This was a direct effect since it was also seen in primary single cell cultures of CD34(2+)CD38- cells. The proliferation of more mature CD34+CD38+ cells, however, was not inhibited by IFN-gamma, demonstrating for the first time that IFN-gamma is a specific and direct hematopoietic stem cell inhibitor. IFN-gamma, moreover, preserves the viability of CD34(2+)CD38- cells in the absence of other cytokines. IFN-gamma could, therefore, play a role in the protection of the stem cell compartment from exhaustion in situations of hematopoietic stress and may be useful as stem cell protecting agent against chemotherapy for cancer.
authors.affiliation: Laboratory of Experimental Hematology, University of Antwerp (UIA) Antwerp University Hospital (UZA), Edegem, Belgium.
authors.forename: H W
authors.initials: HW
authors.lastname: Snoeck
authors.forename: D R
authors.initials: DR
authors.lastname: Van Bockstaele
authors.forename: G
authors.initials: G
authors.lastname: Nys
authors.forename: M
authors.initials: M
authors.lastname: Lenjou
authors.forename: F
authors.initials: F
authors.lastname: Lardon
authors.forename: L
authors.initials: L
authors.lastname: Haenen
authors.forename: I
authors.initials: I
authors.lastname: Rodrigus
authors.forename: M E
authors.initials: ME
authors.lastname: Peetermans
authors.forename: Z N
authors.initials: ZN
authors.lastname: Berneman
mesh_terms: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD / Q000032:analysis*; D018952:Antigens, CD34; D000943:Antigens, Differentiation / Q000032:analysis*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008562:Membrane Glycoproteins
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; D007371:Interferon-gamma; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1