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

Biological effects of tumor necrosis factor cu (TNF-alpha) are mediate d 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 (ant ibodies) 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 g ranulocyte colony-stimulating factor or interleukin 3 alone. In contra st, the 75-kDa TNF receptor is essential in mediating inhibition of pr imitive Lin(-)Sca-1(+) high-proliferative-potential colony-forming cel ls and inhibition of the total number of proliferative clones of indiv idually cultured Lin(-)Sca-1(+)Rh123(lo) and Lin-Sca-1(+)Rh123(hi) cel ls.