Identification of a novel tumor necrosis factor alpha/cachectin from the livers of burned and infected rats.
Tumor necrosis factor alpha (TNF-alpha)/cachectin is a monocyte/macrophage-derived cytokine implicated as a proximal mediator of many of the catastrophic host responses to infection or endotoxin. However, circulating levels of TNF-alpha/cachectin have only been episodically detected in hospitalized patients with life-threatening bacterial infections. In the present report, increased quantities of immune-reactive TNF-alpha/cachectin were recovered from the livers of rats 3 days following a lethal burn and infection. Two species of TNF-alpha/cachectin were detected, one of approximately 29 kd and the other 17 kd, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In murine peritoneal macrophages and rat Kupffer cells stimulated in vitro with endotoxin, a 29-kd cell-associated and 17-kd secreted form were also detected. We conclude that the increased appearance in vivo of a 29-kd form of TNF-alpha/cachectin from the livers of lethally burned and infected rats represents a novel cell-associated form of the protein.
Keogh
C
C
Laboratory of Surgical Metabolism, New York, Hospital-Cornell University Medical College, NY 10021.
Fong
Y
Y
Marano
M A
MA
Seniuk
S
S
He
W
W
Barber
A
A
Minei
J P
JP
Felsen
D
D
Lowry
S F
SF
Moldawer
L L
LL
D000818:Animals; D015153:Blotting, Western; D002056:Burns / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000032:analysis*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D011552:Pseudomonas Infections / Q000378:metabolism*; D011550:Pseudomonas aeruginosa; D051381:Rats; D011919:Rats, Inbred Strains; D012967:Sodium Dodecyl Sulfate; D014409:Tumor Necrosis Factor-alpha / Q000302:isolation & purification*
D014409:Tumor Necrosis Factor-alpha; D012967:Sodium Dodecyl Sulfate