Demonstration of a novel tumor-killing factor secreted from human macrophage-monocyte hybridomas.
We constructed human macrophage-monocyte hybridomas between a thymidine kinase-deficient human macrophage-like cell line, designated as TAM-2, and human peripheral blood monocytes in order for the study of cytokines from human monocytes. The hybrid and macrophage-monocyte nature of the growing cells was confirmed by the following facts: 1) All of the hybridomas established possess TK activity, whereas the TAM-2 cells are TK negative. 2) Most but not all of the hybridomas express the MaG-1 Ag which was shown to be a human macrophage-granulocyte specific Ag, but not T- and B-specific Ag. In the assay for cytokine, a few of the hybridomas produced a novel tumor-killing factor (TKF) after stimulation with PMA, polypeptone, and retinoic acid. Chemical nature of the TKF from the 3-63 hybrid clone was characterized and compared to those of well-known TNF and lymphotoxin. The TKF from a hybridoma was basic protein and had binding capacity to Con A-Sepharose, whereas TNF had an opposite nature. Moreover, TKF activity was not neutralized by both a murine monoclonal antibody against human TNF and rabbit antisera against human lymphotoxin. Thus, these results strongly indicate that the TKF is a novel TKF produced by human monocytic cells.
Taniyama
T
T
Department of Cellular Immunology, National Institute of Health, Tokyo, Japan.
Yoshida
K
K
Furuta
T
T
D002459:Cell Fusion; D002460:Cell Line; D002999:Clone Cells / Q000378:metabolism; D006801:Humans; D006825:Hybridomas / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D010461:Peptones; D013755:Tetradecanoylphorbol Acetate; D014212:Tretinoin; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis*
D010461:Peptones; D014409:Tumor Necrosis Factor-alpha; D014212:Tretinoin; D013755:Tetradecanoylphorbol Acetate