TY - JOUR
T1 - Lethal endotoxic shock using α-galactosylceramide sensitization as a new experimental model of septic shock
AU - Ito, Hiroyasu
AU - Koide, Naoki
AU - Hassan, Ferdaus
AU - Islam, Shamima
AU - Tumurkhuu, Gantsetseg
AU - Mori, Isamu
AU - Yoshida, Tomoaki
AU - Kakumu, Shinichi
AU - Moriwaki, Hisataka
AU - Yokochi, Takashi
N1 - Funding Information:
This work was supported by in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan. We are grateful to Dr T Nakayama and Dr M Taniguchi for providing Va14 NKT-deficient mice and Dr K Saito and Dr K Sekikawa for providing TNF-a-deficient mice. We thank Kirin Brewery Company for providing synthetic a-GalCer. We are also grateful to K Takahashi and A Morikawa for the excellent technical assistance.
PY - 2006/3
Y1 - 2006/3
N2 - 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.
AB - 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.
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U2 - 10.1038/labinvest.3700388
DO - 10.1038/labinvest.3700388
M3 - Article
C2 - 16446706
AN - SCOPUS:33244482534
SN - 0023-6837
VL - 86
SP - 254
EP - 261
JO - Laboratory Investigation
JF - Laboratory Investigation
IS - 3
ER -