Identity of differentiation inducing factor and tumour necrosis factor.
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.
Takeda
K
K
Iwamoto
S
S
Sugimoto
H
H
Takuma
T
T
Kawatani
N
N
Noda
M
M
Masaki
A
A
Morise
H
H
Arimura
H
H
Konno
K
K
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D002454:Cell Differentiation; D002478:Cells, Cultured; D006023:Glycoproteins / Q000032:analysis* / Q000502:physiology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology; D008214:Lymphocytes / Q000502:physiology; D008222:Lymphokines / Q000145:classification / Q000302:isolation & purification* / Q000502:physiology; D009000:Monocytes / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha
D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D008222:Lymphokines; D014409:Tumor Necrosis Factor-alpha