Open AccessRole of the 75-kDa tumor necrosis factor receptor: inhibition of early hematopoiesis.
Author(s) -
Frede W. Jacobsen,
Mike Rothe,
Leiv S. Rusten,
David V. Goeddel,
Erlend B. Smeland,
O. Petter Veiby,
Lars Slørdal,
Sten Eirik W. Jacobsen
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.22.10695
Subject(s) - tumor necrosis factor alpha , receptor , haematopoiesis , biology , cytokine , microbiology and biotechnology , cell surface receptor , cancer research , immunology , endocrinology , stem cell , biochemistry
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.