Identification of a novel tumor necrosis factor alpha/cachectin from the livers of burned and infected rats
C. Keogh, Y. Fong, M. A. Marano, S. Seniuk, W. He, A. Barber, J. P. Minei, D. Felsen, S. F. Lowry and L. L. Moldawer
Laboratory of Surgical Metabolism, New York, Hospital-Cornell University Medical College, NY 10021.
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.
