Role of the 75-kDa Tumor Necrosis Factor Receptor: Inhibition of Early Hematopoiesis

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 91; no. 22; pp. 10695 - 10699
• Main Authors: Jacobsen, Frede W., Rothe, Mike, Rusten, Leiv, Goeddel, David V., Smeland, Erlend B., Veiby, Ole P., Slordal, Lars, Sen E. W. Jacobsen
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 25.10.1994; National Acad Sciences; National Academy of Sciences
• Subjects: Agonists; Animals; Biochemistry; Bone marrow; Bone Marrow Cells; Cell Differentiation - drug effects; Cell Division - drug effects; Cell growth; Cells, Cultured; Colony-Forming Units Assay; Cytokines; Granulocyte Colony-Stimulating Factor - pharmacology; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology; Hematopoiesis; Hematopoiesis - drug effects; Hematopoietic stem cells; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - physiology; Humans; Immunity (Disease); Macrophage Colony-Stimulating Factor - pharmacology; Macrophages; Mice; Mice, Inbred C57BL; Molecular Weight; Progenitor cells; Radioligand Assay; Receptors, Tumor Necrosis Factor - drug effects; Receptors, Tumor Necrosis Factor - physiology; Recombinant Proteins - pharmacology; Tumor necrosis factor receptors; Tumor Necrosis Factor-alpha - pharmacology; Tumors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.22.10695

Biological effects of tumor necrosis factor α (TNF-α) 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-α 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+Rh123loand Lin-Sca-1+Rh123hicells.