Initial characterization of a cytokine which induces differentiation and cytolytic activity in HL-60 promyelocytic leukemia cells: evidence that the cytokine is distinct from other known differentiation-active cytokines.
In this paper we report that, like dimethyl sulfoxide (DMSO), retinoic acid (RA), and conditioned medium (CM) from lectin-stimulated mononuclear leukocytes, CM from a human null cell leukemia line (Reh) induces HL-60 promyelocytic leukemia cells to respond in an enhanced manner to phorbol diester (PDE). Furthermore, Reh-CM induces PDE-resistant HL-60-1E3 cells to respond to PDE and lyse target cells. Additionally, both HL-60 and HL-60-1E3 cells exposed to Reh-CM for 3 days produce superoxide anion and express cell surface antigens present on mature mononuclear phagocytes. No colony-stimulating factor (CSF) or interferon (IFN) activity was detected in Reh-CM, and differentiation activity (DA) was not removed from Reh-CM by insolubilized anti-IFN gamma. While Reh-CM is antiproliferative against a panel of cell lines, its spectrum of activity is different than tumor necrosis factor (TNF) alpha, and neither TNF alpha nor TNF beta inhibit proliferation of HL-60-1E3 or induce these cells to respond to PDE. The differentiation factor (DF) material has been partially purified by ammonium sulfate precipitation and is non-dialyzable; unstable to heat, acid, or alkali treatment; and the activity is not blocked by anti-IL-6 or anti-IFN alpha. The data presented in this paper suggest the presence of a differentiation-inducing factor which is distinct from CSF, IFN alpha or -gamma, TNF alpha, or -beta, or IL-6, which may play a role in the differentiation of malignant (leukemic) and normal cells of the myelomonocytic lineage.
Leftwich
J A
JA
Laboratory of Tumor Immunology, Guthrie Research Institute, Sayre, Pennsylvania 18840-1692.
Hall
R E
RE
D001685:Biological Factors / Q000032:analysis* / Q000302:isolation & purification / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects*; D003115:Colony-Stimulating Factors / Q000032:analysis; D003470:Culture Media; D016207:Cytokines; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D001685:Biological Factors; D003115:Colony-Stimulating Factors; D003470:Culture Media; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D015240:Phorbol 12,13-Dibutyrate; D007371:Interferon-gamma