title: Effects of recombinant tumor necrosis factor on proliferation and differentiation of leukemic and normal hemopoietic cells in vitro. Relationship to cell surface receptor.
abstract: The clonogenic growth of myeloid leukemia cell lines was inhibited by recombinant tumor necrosis factor (rTNF) at 1-15 pM concentration. However, wild type (promyelocytic) HL-60 cells were highly resistant to growth inhibition, but responded with differentiation into monocyte-like cells at 100 pM rTNF. The clonogenic growth of fresh acute myeloid leukemia cells was inhibited by 50% at approximately 15 pM rTNF. The growth of normal granulocyte-macrophage progenitors (CFU-GM) was also inhibited (by 50 pM rTNF), as was the growth of erythroid progenitors (BFU-E) (by 150 pM rTNF). A synergistic antiproliferative effect was demonstrated between rTNF and recombinant interferon-gamma. Use of radioiodinated rTNF enabled us to detect 1,500-2,100 binding sites on myeloid cell lines at 4 degrees C with Kd of approximately 300 pM. At 37 degrees C, the transfer of bound ligand to lysosomes was followed by degradation, inhibited by NH4+. No correlation was observed between the number of binding sites or affinity at 4 degrees C and antiproliferative response to the addition of rTNF.
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006023:Glycoproteins / Q000378:metabolism / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D007457:Iodine Radioisotopes; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000032:analysis*; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D013696:Temperature; D014409:Tumor Necrosis Factor-alpha
chemical_list: D006023:Glycoproteins; D007457:Iodine Radioisotopes; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha