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Interferon gamma receptor deficient mice are resistant to endotoxic shock

Antibody neutralization studies have established interferon gamma (IFN- gamma) as a critical mediator of endotoxic shock. The advent of IFN- gamma receptor negative (IFN gamma R-/-) mutant mice has enabled a more direct assessment of the role of IFN-gamma in endotoxin (lipopolysaccharide [LPS]-induc...

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Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1994
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2191498/
https://www.ncbi.nlm.nih.gov/pubmed/8163930
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collection PubMed
description Antibody neutralization studies have established interferon gamma (IFN- gamma) as a critical mediator of endotoxic shock. The advent of IFN- gamma receptor negative (IFN gamma R-/-) mutant mice has enabled a more direct assessment of the role of IFN-gamma in endotoxin (lipopolysaccharide [LPS]-induced shock. We report that IFN gamma R-/- mice have an increased resistance to LPS-induced toxicity, this resistance manifesting well before the synthesis and release of LPS- induced IFN-gamma. LPS-induced lymphopenia, thrombocytopenia, and weight loss seen in wild-type mice were attenuated in IFN gamma R-/- mice. IFN gamma R-/- mice tolerated 100-1,000 times more LPS than the minimum lethal dose for wild-type mice in a D-galactosamine (D- GalN)/LPS model. Serum tumor necrosis factor (TNF) levels were 10-fold reduced in mutant mice given LPS or LPS/D-GalN. Bone marrow and splenic macrophages from IFN gamma R-/- mice had a four- to sixfold decreased LPS-binding capacity which correlated with similar reduction in CD14. Serum from mutant mice reduced macrophage LPS binding by a further 50%, although LPS binding protein was only 10% reduced. The expression of TNF receptor I (p55) and II (p75) was identical between wild-type and mutant mice. Thus, depressed TNF synthesis, diminished expression of CD14, and low plasma LPS-binding capacity, in addition to blocked IFN- gamma signaling in the mutant mice, likely to combine to manifest in the resistant phenotype of IFN gamma R-/- mice to endotoxin.
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spelling pubmed-21914982008-04-16 Interferon gamma receptor deficient mice are resistant to endotoxic shock J Exp Med Articles Antibody neutralization studies have established interferon gamma (IFN- gamma) as a critical mediator of endotoxic shock. The advent of IFN- gamma receptor negative (IFN gamma R-/-) mutant mice has enabled a more direct assessment of the role of IFN-gamma in endotoxin (lipopolysaccharide [LPS]-induced shock. We report that IFN gamma R-/- mice have an increased resistance to LPS-induced toxicity, this resistance manifesting well before the synthesis and release of LPS- induced IFN-gamma. LPS-induced lymphopenia, thrombocytopenia, and weight loss seen in wild-type mice were attenuated in IFN gamma R-/- mice. IFN gamma R-/- mice tolerated 100-1,000 times more LPS than the minimum lethal dose for wild-type mice in a D-galactosamine (D- GalN)/LPS model. Serum tumor necrosis factor (TNF) levels were 10-fold reduced in mutant mice given LPS or LPS/D-GalN. Bone marrow and splenic macrophages from IFN gamma R-/- mice had a four- to sixfold decreased LPS-binding capacity which correlated with similar reduction in CD14. Serum from mutant mice reduced macrophage LPS binding by a further 50%, although LPS binding protein was only 10% reduced. The expression of TNF receptor I (p55) and II (p75) was identical between wild-type and mutant mice. Thus, depressed TNF synthesis, diminished expression of CD14, and low plasma LPS-binding capacity, in addition to blocked IFN- gamma signaling in the mutant mice, likely to combine to manifest in the resistant phenotype of IFN gamma R-/- mice to endotoxin. The Rockefeller University Press 1994-05-01 /pmc/articles/PMC2191498/ /pubmed/8163930 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Interferon gamma receptor deficient mice are resistant to endotoxic shock
title Interferon gamma receptor deficient mice are resistant to endotoxic shock
title_full Interferon gamma receptor deficient mice are resistant to endotoxic shock
title_fullStr Interferon gamma receptor deficient mice are resistant to endotoxic shock
title_full_unstemmed Interferon gamma receptor deficient mice are resistant to endotoxic shock
title_short Interferon gamma receptor deficient mice are resistant to endotoxic shock
title_sort interferon gamma receptor deficient mice are resistant to endotoxic shock
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2191498/
https://www.ncbi.nlm.nih.gov/pubmed/8163930