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

作者：Yokochi Takashi^*

来源：Innate Immunity, 2012, 18(2): 364-370.

DOI：10.1177/1753425911410236

• LPS
• alpha-galactosylceramide
• interferon-gamma
• endotoxic shock
• NKT cells
• interleukin-4
• experimental model

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 alpha-galactosylceramide (alpha-GalCer)-sensitized mice; the mice died with acute lung injury and respiratory distress within 24 h. alpha-GalCer activates natural killer T (NKT) cells in the lungs and liver, and induces the production of interferon (IFN)-gamma. However, IFN-gamma signaling is only triggered in the lungs and makes them susceptible to LPS. On the other hand, IFN-gamma 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-gamma signaling, in response to alpha-GalCer. The differential cytokine profile between lung and liver NKT cells may lead to organ-specific lung lesions. The experimental system using alpha-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 alpha-GalCer-sensitized mice is provided. In particular, the molecular background of organ-specific development of lung injury in the model is focused on.

• 出版日期2012-4