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Tumor necrosis factor-alpha (TNF-alpha) is a bifunctional regulator of hematopoiesis, and its cellular responses are mediated by two distinct cell surface receptors. TNF-alpha generally inhibits the growth of primitive murine hematopoietic progenitor cells (Lin-Scal+) in response to multiple cytokine combinations, and the p75 TNF receptor is essential in signaling such inhibition. In the present study we show the reverse phenomenon in that TNF-alpha on the same progenitor cell population in combination with stem cell factor (SCF) and interleukin-7 (IL-7) through the p55 TNF receptor can recruit additional progenitors to proliferate. In contrast, TGF-beta 1, another bifunctional regulator of hematopoietic progenitor cell growth, completely blocked SCF plus IL-7-induced proliferation. TNF-alpha increased the number of responding progenitors, as well as the size of the colonies formed. The synergistic effects of TNF-alpha were seen at the single cell level, suggesting that its effects are directly mediated. Finally, whereas SCF plus IL-7 promoted primarily granulopoiesis, the addition of TNF-alpha switched the differentiation toward the production of almost exclusively macrophages.


Journal article



Publication Date





1528 - 1533


Animals, Bone Marrow Cells, Cell Adhesion Molecules, Cell Differentiation, Cell Division, Cells, Cultured, Dose-Response Relationship, Drug, Drug Synergism, Hematopoietic Cell Growth Factors, Hematopoietic Stem Cells, Humans, Interleukin-7, Kinetics, Macrophages, Mice, Mice, Inbred C57BL, Rats, Receptors, Tumor Necrosis Factor, Recombinant Proteins, Stem Cell Factor, Tumor Necrosis Factor-alpha