The type B receptor for tumor necrosis factor-alpha mediates DNA fragmentation in HL-60 and U937 cells and differentiation in HL-60 cells.
Tumor necrosis factor-alpha (TNF) binds to two specific cell surface receptors, types A and B, which are both present on HL-60 and U937 cells, and induces monocytoid differentiation in HL-60 cells and early DNA fragmentation in HL-60 and U937 cells. To further define the receptors' roles, we studied how monoclonal antibodies (MoAbs) against each receptor affected TNF-induced cellular responses. HTR-9, an MoAb against the type B (low affinity, 55 Kd) receptor, reproduced all of these effects in a dose-dependent manner. UTR-1, an MoAb against the type A (high affinity, 75 Kd) receptor, had no effect in saturating doses, but supersaturating doses enhanced DNA fragmentation threefold. TNF and interferon gamma (IFN-gamma) synergistically induced morphologic differentiation and monocytic antigen expression, while the antitype B receptor MoAb was synergistic for morphologic response, but not antigen expression. Our results indicate that (1) the type B receptor mediates some responses to TNF in HL-60 and U937 cells, (2) the type A receptor does not stimulate these responses, (3) the TNF molecule is not necessary for some of these actions, and (4) TNF-induced morphologic changes and surface antigen expression in HL-60 cells may be regulated by separate postreceptor pathways.
Greenblatt
M S
MS
University of New Mexico Cancer Center, Albuquerque 87131-5636.
Elias
L
L
D000911:Antibodies, Monoclonal / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007948:Leukemia, Monocytic, Acute / Q000473:pathology*; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D004247:DNA