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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
Purchase on Springer Link
Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Beisel, W. R. A. Rev. Med. 26, 9–20 (1975).
Filkins, J. P. J. reticuloendothel. Soc. 25, 591–595 (1979); 27, 507–511 (1980); in Patho-physiology of the Reticuloendothelial System (eds Altura, B. M. & Saba, T. M.) 93–110 (Raven, New York, >1981); Fedn Proc. 44, 300–304 (1985).
Dinarello, C. A. New Engl. J. Med. 311, 1413–1418 (1984); in Advances in Inflammation Research 8th edn (ed. Weissmann, G.) 203–225 (Raven, New York, (1984).
Hirsch, R. L., McKay, D. G., Travers, R. I. & Skraly, R. K. J. Lipid Res. 5, 563–568 (1964).
Farshtchi, D. & Lewis, V. J. J. Bact. 95, 1615–1621 (1968).
Gallin, J. I., Kaye, D. & O'Leary, W. M. New Engl. J. Med. 281, 1081–1086 (1969).
Thoen, C. O., Karlson, A. G. & Ellefson, R. D. Mayo Clin. Proc. 47, 258–269, 270–272 (1972).
Guy, M. W. Trans. R. Soc. trop. Med. Hyg. 69, 429 (1975).
Rouzer, C. A. & Cerami, A. Molec. biochem. Parasit. 2, 31–38 (1980).
Kawakami, M. & Cerami, A. J. exp. med. 154, 631–639 (1981).
Kawakami, M., Pekala, P. H., Lane, M. D. & Cerami, A. Proc. natn. Acad. Sci. U.S.A. 79, 912–916 (1982).
Hotez, P. J., Le Trang, N., Fairlamb, A. H. & Cerami, A. Parasite Immun. 6, 203–209 (1984).
Beutler, B., Mahoney, J., Pekala, P., Le Trang, N. & Cerami, A. Blood 64, 65a (1984).
Kawakami, M., Ikeda, Y., Le Trang, N., Vine, W. & Cerami, A. Proc. IUPHAR 2nd edn (ed. Patton, W.) 377–384 (Macmillan, London, 1984).
Beutler, B., Mahoney, J., Le Trang, N., Pekala, P. & Cerami, A. Fedn Proc. 44, 1704 (1985).
Mahoney, J. et al. J. Immun. 134, 1673–1675 (1985).
Beutler, B., Mahoney, J., Le Trang, N., Pekala, P. & Cerami, A. J. exp. Med. 161, 984 (1985).
Pennica, D. et al. Nature 312, 724–729 (1984).
Shirai, T., Yamaguchi, H., Ito, H., Todd, C. W. & Wallace, R. B. Nature 313, 803–806 (1985).
Green, H. & Kehinde, O. Cell 3, 114–116 (1974).
Green, H. & Meuth, M. Cell 3, 127–133 (1974).
Ruff, M. R. & Gifford, G. E. in Lymphokines Vol. 2 (ed. Pick, E.) 235–272 (Academic, New York 1981).
Aggarwal, et al. J. biol. Chem. 260, 2345–2354 (1985).
Pan, Y-C. E., Wideman, J., Blacher, R., Chang, M. & Stein, S. J. Chromatogr. 297, 13–19 (1984).
Pekala, P. H., Kawakami, M., Angus, C. W., Lane, M. D. & Cerami, A. Proc. natn. Acad. Sci. U.S.A. 80, 2743–2747 (1983).
Lefkowitz, R. J., Roth, J. & Pastan, I. Science 170, 633–635 (1970).
Wray, W., Boulikas, T., Wray, V. P. & Hancock, R. Analyt. Biochem. 118, 197–203 (1981).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Beutler, B., Greenwald, D., Hulmes, J. et al. Identity of tumour necrosis factor and the macrophage-secreted factor cachectin. Nature 316, 552–554 (1985). https://doi.org/10.1038/316552a0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/316552a0
This article is cited by
-
Enabling Breastfeeding for Women with Obesity
Current Obstetrics and Gynecology Reports (2023)
-
Effects of combined cannabidiol (CBD) and hops (Humulus lupulus) terpene extract treatment on RAW 264.7 macrophage viability and inflammatory markers
Natural Products and Bioprospecting (2023)
-
Metabolic Messengers: tumour necrosis factor
Nature Metabolism (2021)
-
TNF in the era of immune checkpoint inhibitors: friend or foe?
Nature Reviews Rheumatology (2021)
-
Mikrobiom und Immuntherapien bei Tumorerkrankungen
Wiener klinisches Magazin (2020)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.