TY - JOUR
T1 - Tumor necrosis factor α is a potent synergistic factor for the proliferation of primitive human hematopoietic progenitor cells and induces resistance to transforming growth factor β but not to interferon γ
AU - Snoeck, Hans W.
AU - Weekx, Steven
AU - Moulijn, Aad
AU - Lardon, Filip
AU - Lenjou, Marc
AU - Nys, Griet
AU - Van Ranst, Pascal C.F.
AU - Van Bockstaele, Dirk R.
AU - Berneman, Zwi N.
PY - 1996/2/1
Y1 - 1996/2/1
N2 - Since tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and transforming growth factor (TGF)-β have all been shown to be specific inhibitors of early human hematopoiesis, we wanted to investigate the interactions of these three cytokines on very primitive human adult bone marrow CD34++CD38- hematopoietic progenitor cells, using a pre-colony-forming cell (pre-CFC) assay, which detects the effects of these cytokines on the initial phases of the differentiation of these primitive progenitors, which are unresponsive to interleukin (IL) 3 alone. Surprisingly, TNF-α was a very potent stimulator of the proliferation of CD34++CD38- cells and was the most potent synergistic factor for the IL-3-induced proliferation of these cells of all cytokines tested (IL-1, IL-6, granulocyte colony-stimulating factor, kit ligand). TNF-α was the only cytokine that, as a single added factor, induced substantial proliferation in CD34++CD38- cells in the presence of IL-3, except for kit ligand, which induced very limited proliferation. TNF-α, moreover, induced a high degree of resistance to the inhibitory effects of TGF-β in a dose-dependent way. The inhibitory effects of IFN-γ, however, were not affected by the presence of TNF-α. We hypothesize that in situations of hematopoietic stress, TNF-α may abrogate the inhibitory effect of ambient TGF-β in the bone marrow microenvironment to allow primitive stem cells to proliferate and differentiate in response to an increased demand for mature blood cells.
AB - Since tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and transforming growth factor (TGF)-β have all been shown to be specific inhibitors of early human hematopoiesis, we wanted to investigate the interactions of these three cytokines on very primitive human adult bone marrow CD34++CD38- hematopoietic progenitor cells, using a pre-colony-forming cell (pre-CFC) assay, which detects the effects of these cytokines on the initial phases of the differentiation of these primitive progenitors, which are unresponsive to interleukin (IL) 3 alone. Surprisingly, TNF-α was a very potent stimulator of the proliferation of CD34++CD38- cells and was the most potent synergistic factor for the IL-3-induced proliferation of these cells of all cytokines tested (IL-1, IL-6, granulocyte colony-stimulating factor, kit ligand). TNF-α was the only cytokine that, as a single added factor, induced substantial proliferation in CD34++CD38- cells in the presence of IL-3, except for kit ligand, which induced very limited proliferation. TNF-α, moreover, induced a high degree of resistance to the inhibitory effects of TGF-β in a dose-dependent way. The inhibitory effects of IFN-γ, however, were not affected by the presence of TNF-α. We hypothesize that in situations of hematopoietic stress, TNF-α may abrogate the inhibitory effect of ambient TGF-β in the bone marrow microenvironment to allow primitive stem cells to proliferate and differentiate in response to an increased demand for mature blood cells.
UR - http://www.scopus.com/inward/record.url?scp=0030024423&partnerID=8YFLogxK
U2 - 10.1084/jem.183.2.705
DO - 10.1084/jem.183.2.705
M3 - Article
C2 - 8627186
AN - SCOPUS:0030024423
SN - 0022-1007
VL - 183
SP - 705
EP - 710
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 2
ER -