Identity of tumour necrosis factor and the macrophage-secreted factor cachectin

• Published in: Nature (London) 1985-08, Vol.316 (6028), p.552-554
• Main Authors: Beutler, B, Greenwald, D, Hulmes, J. D, Chang, M, Pan, Y.-C. E, Mathison, J, Ulevitch, R, Cerami, A
• Format: Article
• Language: English
• Subjects: Adipose Tissue - metabolism; Amino Acid Sequence; Amino Acids - analysis; Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Glycoproteins - isolation & purification; Humanities and Social Sciences; letter; Lipoprotein Lipase - antagonists & inhibitors; Macrophages - physiology; Mice; multidisciplinary; Protein hormones. Growth factors. Cytokines; Proteins; Proteins - isolation & purification; Receptors, Cell Surface - physiology; Receptors, Tumor Necrosis Factor; Science; Tumor Necrosis Factor-alpha
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/316552a0

In mammals, several well-defined metabolic changes occur during infection, many of which are attributable to products of the reticuloendothelial system 1–3 . Among these changes, a hypertrigly-ceridaemic state is frequently evident 4–9 , resulting from defective triglyceride clearance, caused by systemic suppression of the enzyme lipoprotein lipase (LPL) 9 . We have found previously that macrophages secrete the hormone cachectin, which specifically suppresses LPL activity in cultured adipocytes (3T3-L1 cells) 10–17 . When originally purified from RAW 264.7 (mouse macrophage) cells, cachectin was shown to have a p I of 4.7, a subunit size of relative molecular mass ( M r ) 17,000 and to form non-covalent multimers 17 . A receptor for cachectin was identified on non-tumorigenic cultured cells and on normal mouse liver membranes 17 . A new high-yield purification technique has enabled us to determine further details of the structure of mouse cachectin. We now report that a high degree of homology exists between the N-terminal sequence of mouse cachectin and the N-terminal sequence recently determined for human tumour necrosis factor (TNF) 18,19 . Purified cachectin also possesses potent TNF activity in vitro . These findings suggest that the ‘cachectin’ and ‘TNF’ activities of murine macrophage conditioned medium are attributable to a single protein, which modulates the metabolic activities of normal as well as neoplastic cells through interaction with specific high-affinity receptors.