Interferon gamma receptor deficient mice are resistant to endotoxic shock.

Détails

ID Serval
serval:BIB_BD1CB73A665A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Interferon gamma receptor deficient mice are resistant to endotoxic shock.
Périodique
Journal of Experimental Medicine
Auteur(s)
Car B.D., Eng V.M., Schnyder B., Ozmen L., Huang S., Gallay P., Heumann D., Aguet M., Ryffel B.
ISSN
0022-1007 (Print)
ISSN-L
0022-1007
Statut éditorial
Publié
Date de publication
1994
Volume
179
Numéro
5
Pages
1437-1444
Langue
anglais
Résumé
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.
Mots-clé
Animals, Body Weight, Endotoxins, Immunity, Innate, Lipopolysaccharides/toxicity, Mice, Molecular Sequence Data, Receptors, Interferon/deficiency, Receptors, Interferon/immunology, Shock, Septic/immunology, Tumor Necrosis Factor-alpha/analysis
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/01/2008 12:36
Dernière modification de la notice
09/05/2019 0:32
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