title: A new experimental murine model for lipopolysaccharide-mediated lethal shock with lung injury.
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.
authors.affiliation: Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan. yokochi@aichi-med-u.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokochi
mesh_terms: D055371:Acute Lung Injury / Q000503:physiopathology*; D000818:Animals; D004195:Disease Models, Animal; D005699:Galactosylceramides / Q000276:immunology / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000502:physiology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000502:physiology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D012772:Shock, Septic / Q000503:physiopathology*
chemical_list: D005699:Galactosylceramides; D008070:Lipopolysaccharides; C493154:alpha-galactosylceramide; D015847:Interleukin-4; D007371:Interferon-gamma