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Biological effects of tumor necrosis factor alpha (TNF-alpha) are mediated through two cell surface receptors, the 55-kDa TNF receptor and the 75-kDa TNF receptor. The present study investigated the relative roles of the two TNF receptors in normal hematopoiesis. Using agonists (antibodies) specific for the 55- and 75-kDa TNF receptors, we demonstrate differential roles of the two TNF receptors in hematopoiesis in that only the 55-kDa TNF receptor mediates antiproliferative effects of TNF-alpha on mature Lin- hematopoietic progenitor cells responding to granulocyte colony-stimulating factor or interleukin 3 alone. In contrast, the 75-kDa TNF receptor is essential in mediating inhibition of primitive Lin-Sca-1+ high-proliferative-potential colony-forming cells and inhibition of the total number of proliferative clones of individually cultured Lin-Sca-1+Rh123lo and Lin-Sca-1+Rh123hi cells.

Original publication




Journal article


Proc Natl Acad Sci U S A

Publication Date





10695 - 10699


Animals, Bone Marrow Cells, Cell Differentiation, Cell Division, Cells, Cultured, Colony-Forming Units Assay, Granulocyte Colony-Stimulating Factor, Granulocyte-Macrophage Colony-Stimulating Factor, Hematopoiesis, Hematopoietic Stem Cells, Humans, Macrophage Colony-Stimulating Factor, Mice, Mice, Inbred C57BL, Molecular Weight, Radioligand Assay, Receptors, Tumor Necrosis Factor, Recombinant Proteins, Tumor Necrosis Factor-alpha