Identity of tumour necrosis factor and the macrophage-secreted factor cachectin.
In mammals, several well-defined metabolic changes occur during infection, many of which are attributable to products of the reticuloendothelial system. Among these changes, a hypertriglyceridaemic state is frequently evident, resulting from defective triglyceride clearance, caused by systemic suppression of the enzyme lipoprotein lipase (LPL). We have found previously that macrophages secrete the hormone cachectin, which specifically suppresses LPL activity in cultured adipocytes (3T3-L1 cells). 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 multimers. A receptor for cachectin was identified on non-tumorigenic cultured cells and on normal mouse liver membranes. 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). 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.
Beutler
B
B
Greenwald
D
D
Hulmes
J D
JD
Chang
M
M
Pan
Y C
YC
Mathison
J
J
Ulevitch
R
R
Cerami
A
A
D000273:Adipose Tissue / Q000378:metabolism; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D006023:Glycoproteins / Q000302:isolation & purification; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D011506:Proteins / Q000302:isolation & purification; D011956:Receptors, Cell Surface / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha
D000596:Amino Acids; D006023:Glycoproteins; D011506:Proteins; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D008071:Lipoprotein Lipase