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

B. Beutler, D. Greenwald, J. D. Hulmes, M. Chang, Y. C E Pan, J. Mathison, R. Ulevitch, A. Cerami

Research output: Contribution to journalArticle

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Abstract

In mammals, several well-defined metabolic changes occur during infection, many of which are attributable to products of the reticuloendothelial system1-3. Among these changes, a hypertrigly-ceridaemic state is frequently evident4-9, 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 pI of 4.7, a subunit size of relative molecular mass (Mr) 17,000 and to form non-covalent multimers17. A receptor for cachectin was identified on non-tumorigenic cultured cells and on normal mouse liver membranes17. 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.

Original languageEnglish (US)
Pages (from-to)552-554
Number of pages3
JournalNature
Volume316
Issue number6028
DOIs
StatePublished - 1985

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Tumor Necrosis Factor-alpha
Macrophages
Lipoprotein Lipase
3T3-L1 Cells
Tumor Necrosis Factor Receptors
Conditioned Culture Medium
Adipocytes
Cell Communication
Mammals
Cultured Cells
Triglycerides
Hormones
Liver
Enzymes
Infection
Proteins

ASJC Scopus subject areas

  • General

Cite this

Beutler, B., Greenwald, D., Hulmes, J. D., Chang, M., Pan, Y. C. E., Mathison, J., ... Cerami, A. (1985). Identity of tumour necrosis factor and the macrophage-secreted factor cachectin. Nature, 316(6028), 552-554. https://doi.org/10.1038/316552a0

Identity of tumour necrosis factor and the macrophage-secreted factor cachectin. / Beutler, B.; Greenwald, D.; Hulmes, J. D.; Chang, M.; Pan, Y. C E; Mathison, J.; Ulevitch, R.; Cerami, A.

In: Nature, Vol. 316, No. 6028, 1985, p. 552-554.

Research output: Contribution to journalArticle

Beutler, B, Greenwald, D, Hulmes, JD, Chang, M, Pan, YCE, Mathison, J, Ulevitch, R & Cerami, A 1985, 'Identity of tumour necrosis factor and the macrophage-secreted factor cachectin', Nature, vol. 316, no. 6028, pp. 552-554. https://doi.org/10.1038/316552a0
Beutler B, Greenwald D, Hulmes JD, Chang M, Pan YCE, Mathison J et al. Identity of tumour necrosis factor and the macrophage-secreted factor cachectin. Nature. 1985;316(6028):552-554. https://doi.org/10.1038/316552a0
Beutler, B. ; Greenwald, D. ; Hulmes, J. D. ; Chang, M. ; Pan, Y. C E ; Mathison, J. ; Ulevitch, R. ; Cerami, A. / Identity of tumour necrosis factor and the macrophage-secreted factor cachectin. In: Nature. 1985 ; Vol. 316, No. 6028. pp. 552-554.
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