Identity of differentiation inducing factor and tumour necrosis factor

• Published in: Nature (London) Vol. 323; no. 6086; p. 338
• Main Authors: Takeda, K, Iwamoto, S, Sugimoto, H, Takuma, T, Kawatani, N, Noda, M, Masaki, A, Morise, H, Arimura, H, Konno, K
• Format: Journal Article
• Language: English
• Published: England 25.09.1986
• Subjects: Amino Acid Sequence; Antibodies, Monoclonal; Cell Differentiation; Cells, Cultured; Glycoproteins - analysis; Glycoproteins - physiology; Humans; Leukemia, Myeloid, Acute - pathology; Lymphocytes - physiology; Lymphokines - classification; Lymphokines - isolation & purification; Lymphokines - physiology; Monocytes - physiology; Tumor Necrosis Factor-alpha
• ISSN: 0028-0836
• DOI: 10.1038/323338a0

Human myelogenous leukaemic cells can be induced to differentiate into the monocyte/macrophage pathway by protein inducers called differentiation inducing factors (DIF) in conditioned media of mitogen-stimulated human peripheral blood leukocytes. However, human DIF has not yet been well characterized. DIF is known to be a T-cell lymphokine, as it can be obtained from the T-cell line HUT-102 and can be partially purified from medium conditioned by phytohaemagglutinin (PHA)-stimulated lymphocytes. We found that monocytes also produce factor(s) that induce differentiation of human myelogenous leukaemia cell lines to cells with macrophage-like characteristics. This factor(s) has activity different from that of colony-stimulating factor(s) or interferons. We have now purified a DIF to homogeneity from medium conditioned by PHA-stimulated leukocytes using a human myeloblastic leukemia cell line, ML-1, as target cells. The purified DIF has a relative molecular mass (Mr) of approximately 17,000, with an NH2-terminal sequence the same as that of human tumour necrosis factor (TNF). Recombinant human TNF (rHuTNF) induces differentiation of ML-1 cells and an anti-pDIF monoclonal antibody can neutralize both differentiation inducing activity and cytotoxic activity of DIF and rHuTNF. The findings indicate that one of the DIF(s) produced by leukocytes is probably TNF.