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Title: Differential response of a(2)-macroglobulin-deficient mice in models of lethal TNF-induced inflammation
Authors: Hochepied, T ×
Ameloot, Paul
Brouckaert, P
Van Leuven, Freddy
Libert, C #
Issue Date: Jan-2001
Series Title: European cytokine network. vol:11 issue:4 pages:597-601
Abstract: Tumor necrosis factor (TNF) is an essential mediator in the pathogenesis of Gram-negative septic shock. Injection of TNF into normal mice leads to systemic, lethal inflammation, which is indistinguishable from lipopolysaccharide (LPS)-induced lethal inflammation. alpha(2)-macroglobulin (A2M) is a major positive acute phase protein with broad-spectrum protease-inhibitory activity. Mouse A2M-deficient (MAM-/-) mice were significantly protected against lethal systemic inflammation induced by TNF. The protection is not due to faster clearance of the injected TNF. The induction of tolerance to TNF-induced lethality by repetitive administration of small doses of human TNF for five consecutive days was equally efficient in both mutant mice compared to wild-type mice. In D-(+)-galactosamine (GalN)-sensitized mice, TNF induces lethal inflammatory hepatitis. MAM(-/-) mice are equally sensitive to the lethal combination of TNF/GalN. Furthermore, interleukin-1-induced desensitization to TNF/GalN was not impaired in MAM(-/-) mice. We conclude that MAM plays a mediating role in TNF-induced lethal shock and that MAM deficiency does not reduce changes in efficiency of tolerance and desensitization to TNF and TNF/GalN-induced lethality, respectively.
ISSN: 1148-5493
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Associated Laboratories - miscellaneous (-)
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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