ROLE OF THE 75-KDA TUMOR-NECROSIS-FACTOR RECEPTOR - INHIBITION OF EARLY HEMATOPOIESIS

Biological effects of tumor necrosis factor cu (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(+)Rh123(lo) and Lin-Sca-1(+)Rh123(hi) cells.