TUMOR NECROSIS FACTOR-ALPHA STRONGLY POTENTIATES INTERLEUKIN-3 AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR-INDUCED PROLIFERATION OF HUMAN CD34+ HEMATOPOIETIC PROGENITOR CELLS

  • 15 June 1990
    • journal article
    • research article
    • Vol. 75  (12) , 2292-2298
Abstract
Previous studies have shown that tumor necrosis factors (TNFs) inhibit the proliferative effects of crude or purified colony-stimulating factors (CSFs) on low density human bone marrow cell fractions. In the present study we investigated the effects of TNF.alpha. on the growth of highly purified CD34+ human hematopoietic progenitor cells (HPC) in response to recombinant CSFs. In short-term liquid cultures (5 to 8 days), TNF.alpha. strongly potentiates interleukin-3 (IL-3) and granulocyte-macrophage-CSF (GM-CSF)-induced growth of CD34+ HPC, while it has no proliferative effect per se. Within 8 days, the number of viable cells obtained in TNF.alpha.-supplemented cultures is threefold higher than in cultures carried out with IL-3 -induced proliferation of CD34+ HPC does not result from an IL-3-dependent generation of TNF.alpha. responsive cells. Limiting dilution analysis indicates that TNF.alpha. increases both the frequency of IL-3 responding cells and the average size of the IL-3 responding cells and the average size of the IL-3-dependent clones. The potentiating effect of TNF.alpha. on IL-3- and GM-CSF-dependent growth of CD34+ HPC is also observed in day 7 colony assays. Under these short-term culture conditions. TNF.alpha. does not appear to accelerate cell maturation as a precursor morphology is retained. Finally, TNF.alpha. inhibits the relatively weak growth-promoting effect of granulocyte-CSF (G-CSF), which acts on a more committed subpopulation of CD34+ HPC different from that recruited by IL-3 and GM-CSF. TNF.beta. displays the same modulatory effects as TNF.alpha.. Thus, TNFs appear to enhance the early stages of myelopoiesis.

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