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Innate Immun. 2012 Apr;18(2):364-70. doi: 10.1177/1753425911410236. Epub 2011 Jul 29.

A new experimental murine model for lipopolysaccharide-mediated lethal shock with lung injury.

Author information

1
Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan. yokochi@aichi-med-u.ac.jp

Abstract

We have recently established a new experimental murine model for lipopolysaccharide (LPS)-mediated lethal shock with lung-specific injury. Severe lung injury is induced by administration of LPS into α-galactosylceramide (α-GalCer)-sensitized mice; the mice died with acute lung injury and respiratory distress within 24 h. α-GalCer activates natural killer T (NKT) cells in the lungs and liver, and induces the production of interferon (IFN)-γ. However, IFN-γ signaling is only triggered in the lungs and makes them susceptible to LPS. On the other hand, IFN-γ signaling is inhibited in liver and results in few hepatic lesions. Unlike liver NKT cells, lung NKT cells fail to produce interleukin (IL)-4, which down-regulates the IFN-γ signaling, in response to α-GalCer. The differential cytokine profile between lung and liver NKT cells may lead to organ-specific lung lesions. The experimental system using α-GalCer sensitization could be a useful experimental model for clinical endotoxic or septic shock as it presents respiratory failure, a typical manifestation in severe septic patients. In this review, key evidence and the introducuction of the detailed mechanism of LPS-mediated lung-specific injury in α-GalCer-sensitized mice is provided. In particular, the molecular background of organ-specific development of lung injury in the model is focused on.

PMID:
21803777
DOI:
10.1177/1753425911410236
[Indexed for MEDLINE]

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