Lethal endotoxic shock using α-galactosylceramide sensitization as a new experimental model of septic shock

Hiroyasu Ito, Naoki Koide, Ferdaus Hassan, Shamima Islam, Gantsetseg Tumurkhuu, Isamu Mori, Tomoaki Yoshida, Shinichi Kakumu, Hisataka Moriwaki, Takashi Yokochi

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

Abstract

The effect of α-galactosylceramide (α-GalCer) on lipopolysaccharide (LPS)-mediated lethality was examined. Administration of LPS killed all mice pretreated with α-GalCer, but not untreated control mice. The lethal shock in α-GalCer-sensitized mice was accompanied by severe pulmonary lesions with marked infiltration of inflammatory cells and massive cell death. On the other hand, hepatic lesions were focal and mild. A number of cells in pulmonary and hepatic lesions underwent apoptotic cell death. α-GalCer sensitization was ineffective for the development of the systemic lethal shock in Vα14-positive natural killer T cell-deficient mice. Sensitization with α-GalCer led to the circulation of a high level of interferon (IFN)-γ and further augmented the production of tumor necrosis factor (TNF)-α in response to LPS. The lethal shock was abolished by the administration of anti-IFN-γ or TNF-α antibody. Further, the lethal shock did not occur in TNF-α-deficient mice. Taken together, α-GalCer sensitization rendered mice very susceptible to LPS-mediated lethal shock, and IFN-γ and TNF-α were found to play a critical role in the preparation and execution of the systemic lethal shock, respectively. The LPS-mediated lethal shock using α-GalCer sensitization might be useful for researchers employing experimental models of sepsis and septic shock.

Original languageEnglish
Pages (from-to)254-261
Number of pages8
JournalLaboratory Investigation
Volume86
Issue number3
DOIs
Publication statusPublished - 03-2006

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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