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

Hans W. Snoeck, Steven Weekx, Aad Moulijn, Filip Lardon, Marc Lenjou, Griet Nys, Pascal C.F. Van Ranst, Dirk R. Van Bockstaele, Zwi N. Berneman

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49 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)705-710
Number of pages6
JournalJournal of Experimental Medicine
Volume183
Issue number2
DOIs
StatePublished - 1 Feb 1996
Externally publishedYes

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