Identification of components of differentiation-inducing activity of human T-cell lymphoma cells by induction of differentiation in human myeloid leukemia cells.
Two lymphokines that contribute to induction of cell differentiation in promyelocytic HL-60 leukemia cells by human T-cell lymphoma HUT-102 cells were identified previously. The lymphokines identified in the differentiation-inducing preparation were interferon-gamma (IFN-gamma) and lymphotoxin. To determine the remaining component(s) of this differentiation-inducing activity, we used gene-cloned (recombinant) forms and antibodies of lymphokines. The differentiation-inducing activity of the HUT-102 cells was not completely neutralized by the antibodies, suggesting that an additional lymphokine(s) is involved. Granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with retinoic acid induced differentiation of the HL-60 cells in a dose-dependent manner. Furthermore, the activity of the differentiation-inducing factors was partially inhibited by anti-GM-CSF antibody and completely inhibited by the combination of antibodies to lymphotoxin, IFN-gamma, and GM-CSF. These results indicate that, in addition to IFN-gamma and lymphotoxin, GM-CSF is the third major component released by HUT-102 cells for inducing differentiation of HL-60 cells.
Hemmi
H
H
Department of Bacteriology, Tohoku University School of Medicine, Sendai, Japan.
Nakamura
T
T
Shimizu
Y
Y
Sugamura
K
K
D002454:Cell Differentiation / Q000187:drug effects; D002852:Chromatography, Ion Exchange; D003115:Colony-Stimulating Factors / Q000096:biosynthesis* / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000096:biosynthesis* / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D008223:Lymphoma / Q000378:metabolism*; D008233:Lymphotoxin-alpha / Q000096:biosynthesis* / Q000494:pharmacology; D009500:Neutralization Tests; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007375:Interleukin-1; D008233:Lymphotoxin-alpha; D011994:Recombinant Proteins; D014212:Tretinoin; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor