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Alpha 1-acid glycoprotein and alpha 1-antitrypsin inhibit TNF-induced but not anti-Fas-induced apoptosis of hepatocytes in mice.

W Van Molle, C Libert, W Fiers and P Brouckaert
J Immunol October 1, 1997, 159 (7) 3555-3564;
W Van Molle
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C Libert
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W Fiers
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P Brouckaert
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Abstract

The acute phase proteins alpha 1-acid glycoprotein (alpha 1-AGP) and alpha 1-antitrypsin (alpha 1-AT) were shown to inhibit, by a mechanism unidentified to date, the lethality induced by TNF both in normal mice and in mice sensitized with galactosamine. We found that both bovine alpha 1-AGP and human alpha 1-AT also inhibited specifically the induction of apoptosis of hepatocytes by TNF/ galactosamine in vivo. This inhibition is specific for TNF, since apoptosis induced by TNF and actinomycin D was also inhibited, while similar apoptosis of hepatocytes induced by anti-Fas remained unaffected. The observation that these acute phase proteins did not affect the induction by TNF of IL-6, nitric oxide, or serum amyloid P excludes a nonselective inhibition of the TNF-activated pathways. The protection conferred by alpha 1-AGP and alpha 1-AT is presumably indirect, since these proteins did not inhibit TNF/actinomycin D-induced apoptosis in the hepatoma cell lines HepG2 and BWTG3.

  • Copyright © 1997 by American Association of Immunologists
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The Journal of Immunology
Vol. 159, Issue 7
1 Oct 1997
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Alpha 1-acid glycoprotein and alpha 1-antitrypsin inhibit TNF-induced but not anti-Fas-induced apoptosis of hepatocytes in mice.
W Van Molle, C Libert, W Fiers, P Brouckaert
The Journal of Immunology October 1, 1997, 159 (7) 3555-3564;

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Alpha 1-acid glycoprotein and alpha 1-antitrypsin inhibit TNF-induced but not anti-Fas-induced apoptosis of hepatocytes in mice.
W Van Molle, C Libert, W Fiers, P Brouckaert
The Journal of Immunology October 1, 1997, 159 (7) 3555-3564;
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Print ISSN 0022-1767        Online ISSN 1550-6606