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
Institution
Titre
Interferon gamma receptor deficient mice are resistant to endotoxic shock.
Périodique
Journal of Experimental Medicine
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 11:36
Dernière modification de la notice
20/08/2019 15:31