Detection and localization of tumor necrosis factor in human atheroma

doi:10.1016/0002-9149(90)90291-8

The American Journal of Cardiology

Volume 65, Issue 5, 1 February 1990, Pages 297-302

https://doi.org/10.1016/0002-9149(90)90291-8 Get rights and content

Abstract

Tumor necrosis factor (TNF) is a secretory product of normal macrophages that can cause cell necrosis, new blood vessel formation and thrombosis. These are also 3 characteristic features of the progression of stable atheroma to endothelial disruption. Accordingly, an immunohistochemical method was developed to detect TNF in human tissue. Using this method TNF positivity was demonstrated in 57 of 65 (88%) of tissue sections classified as atherosclerotic and in 5 of 11 (45%) sections classified as minimally atherosclerotic. TNF was absent in 6 sections classified as normal. TNF positivity was found not only in the cytoplasm of macrophages, but also in the cytoplasm and attached to the cell membrane of smooth muscle cells and endothelial cells of the human atheroma. Because TNF is known to cause new vessel formation, hemorrhagic necrosis and increased thrombogenecity, it may play a role in the evolution of uncomplicated to complex atheroma.

References (26)

RR Schleef et al.
Cytokine activation of vascular endothelium. Effects on tissue-type plasminogen activator and type 1 plasminogen activator inhibitor
J Biol Chem
(1988)
PL Ey et al.
Isolation of pure IgG, IgG_2a and IgG_2b immunoglobulins from mouse serum using protein A-sepharose
Immunochemistry
(1978)
WH Burnette
Western blotting: Electrophoretic transfer of proteins from SDS-polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A
Anal Biochem
(1981)
D Mannel et al.
Macrophages as a source of tumoricidal activity (tumor necrosis factor)
Infect Immun
(1980)
BA Beutler et al.
Cachectin and tumor necrosis factor as two sides of the same biological coin
Nature
(1986)
SJ Leibovich et al.
Macrophage-induced angiogenesis is mediated by tumor necrosis factor
Nature
(1987)
T Kawai et al.
Necrotizing activity of tumor necrosis factor: histopathological investigation using Meth A sarcoma and granulation tissue
Virchows Arch B
(1987)
N Watanabe et al.
Toxic effect of tumor necrosis factor on tumor vasculature in mice
Cancer Res
(1988)
JWM Van der Meer et al.
Concentrations of immunoreactive human tumor necrosis factor alpha produced by human mononuclear cells in vitro
J Leukocyte Biol
(1988)
PP Nawroth et al.
Modulation of endothelial cell hemostatic properties by tumor necrosis factor
Exp Med
(1986)

MP Bevilacqua et al.

Recombinant tumor necrosis factor induces procoagulant activity in cultured human vascular endothelium: characterization and comparison with the actions of interleukin 1

MI Cybulsky et al.

Biology of disease. Acute inflammation and microthrombosis induced by endotoxin, interleukin-1, and tumor necrosis factor and their implication in gram-negative infection

Lab Invest

(1988)

AC Barger et al.

Hypothesis: vasa vasorum and neovascularization of human coronary arteries. A possible role in pathophysiology of atherosclerosis

N Engl J Med

(1984)

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Detection and localization of tumor necrosis factor in human atheroma

Abstract

J Biol Chem

Immunochemistry

Anal Biochem

Macrophages as a source of tumoricidal activity (tumor necrosis factor)

Infect Immun

Cachectin and tumor necrosis factor as two sides of the same biological coin

Nature

Macrophage-induced angiogenesis is mediated by tumor necrosis factor

Nature

Necrotizing activity of tumor necrosis factor: histopathological investigation using Meth A sarcoma and granulation tissue

Virchows Arch B

Toxic effect of tumor necrosis factor on tumor vasculature in mice

Cancer Res

Concentrations of immunoreactive human tumor necrosis factor alpha produced by human mononuclear cells in vitro

J Leukocyte Biol

Modulation of endothelial cell hemostatic properties by tumor necrosis factor

Exp Med

Recombinant tumor necrosis factor induces procoagulant activity in cultured human vascular endothelium: characterization and comparison with the actions of interleukin 1

Biology of disease. Acute inflammation and microthrombosis induced by endotoxin, interleukin-1, and tumor necrosis factor and their implication in gram-negative infection

Lab Invest

Hypothesis: vasa vasorum and neovascularization of human coronary arteries. A possible role in pathophysiology of atherosclerosis

N Engl J Med