Low susceptibility of NC/Nga mice to the lipopolysaccharide-mediated lethality with d-galactosamine sensitization and the involvement of fewer natural killer T cells

The LPS-mediated lethality of NC/Nga mice, having fewer NKT cells, was examined by using d-galactosamine (d-GalN)-sensitization. The NC/Nga mice were not killed by a simultaneous administration of d-GalN and LPS whereas all C57BL/6 (B6) control mice were killed. The injection of d-GalN and LPS failed to elevate the levels of serum alanine aminotransferase and caspase 3 in the liver tissues of NC/Nga mice. Further, the nitric oxide (NO) level of the d-GalN- and LPS-injected NC/Nga mice was much lower than those of the B6 mice. The expression of an inducible NO synthase (iNOS) was significantly reduced in the livers of NC/Nga mice. However, there was no significant difference in LPS-induced TNF-α production between B6 mice and NC/Nga mice. The NC/Nga mice had an impaired expression of IFN-γ protein and mRNA in response to d-GalN and LPS. The pretreatment with α-galactosylceramide (α-GalCer), which activates Vα14+ NKT cells and induces the production of IFN-γ, rendered NC/Nga mice more susceptible to the LPS-mediated lethality. The livers of NC/Nga mice had fewer NKT cells compared to B6 mice. Taken together, it is suggested that the resistance of NC/Nga mice to the LPS-mediated lethality with d-GalN sensitization depended on the impaired IFN-γ production caused by fewer NKT cells and reduced NO production that followed.

[1]  K. Kabashima,et al.  Sustained Exogenous Expression of Therapeutic Levels of IFN-γ Ameliorates Atopic Dermatitis in NC/Nga Mice via Th1 Polarization , 2010, The Journal of Immunology.

[2]  S. Tanabe,et al.  Oral administration of a galactooligosaccharide preparation inhibits development of atopic dermatitis-like skin lesions in NC/Nga mice. , 2010, International Journal of Molecular Medicine.

[3]  N. Koide,et al.  Low susceptibility of NC/Nga mice to tumor necrosis factor-alpha-mediated lethality and hepatocellular damage with D-galactosamine sensitization. , 2009, Clinical immunology.

[4]  F. Hassan,et al.  The mechanism of development of acute lung injury in lethal endotoxic shock using α‐galactosylceramide sensitization , 2008, Clinical and experimental immunology.

[5]  F. Hassan,et al.  Lipopolysaccharide enhances interferon-γ-induced nitric oxide (NO) production in murine vascular endothelial cells via augmentation of interferon regulatory factor-1 activation , 2007, Journal of endotoxin research.

[6]  K. H. Kim,et al.  Suppression of spontaneous dermatitis in NC/Nga murine model by PG102 isolated from Actinidia arguta. , 2007, The Journal of investigative dermatology.

[7]  N. Shinomiya,et al.  Mice deficient in Vβ8+NKT cells are resistant to experimental hepatitis but are partially susceptible to generalised Shwartzman reaction , 2007, Clinical and Experimental Medicine.

[8]  F. Hassan,et al.  Lethal endotoxic shock using α-galactosylceramide sensitization as a new experimental model of septic shock , 2006, Laboratory Investigation.

[9]  F. Hassan,et al.  Augmentation of lipopolysaccharide-induced nitric oxide production by α-galactosylceramide in mouse peritoneal cells , 2005, Journal of endotoxin research.

[10]  S. Seki,et al.  A murine model of NKT cell-mediated liver injury induced by alpha-galactosylceramide/d-galactosamine , 2005, Virchows Archiv.

[11]  寺田 信.  Contribution of IL-18 to atopic-dermatitis-like skin inflammation induced by Staphylococcus aureus product in mice , 2005 .

[12]  T. Shiohara,et al.  Animal models for atopic dermatitis: are they relevant to human disease? , 2004, Journal of dermatological science.

[13]  K. Nishioka,et al.  Therapeutic effects of streptococcal preparation OK-432 on atopic dermatitis-like lesions in NC/Nga mice: possible shift from a Th2- to Th1-predominance. , 2004, Journal of dermatological science.

[14]  Hiroyuki Tanaka,et al.  Establishment of allergic dermatitis in NC/Nga mice as a model for severe atopic dermatitis. , 2004, Biological & pharmaceutical bulletin.

[15]  K Mihara,et al.  Vital role of the itch–scratch response in development of spontaneous dermatitis in NC/Nga mice , 2004, The British journal of dermatology.

[16]  R. Silverstein.  Review: D-Galactosamine lethality model: scope and limitations , 2004 .

[17]  R. Silverstein.  D-galactosamine lethality model: scope and limitations. , 2004, Journal of endotoxin research.

[18]  S. Fan,et al.  STAT1 plays an essential role in LPS/D-galactosamine-induced liver apoptosis and injury. , 2003, American journal of physiology. Gastrointestinal and liver physiology.

[19]  H. Matsuda,et al.  Inability of IL-12 to Down-Regulate IgE Synthesis Due to Defective Production of IFN-γ in Atopic NC/Nga Mice1 , 2001, The Journal of Immunology.

[20]  M. Smyth,et al.  Cytometric and functional analyses of NK and NKT cell deficiencies in NOD mice. , 2001, International immunology.

[21]  T. Majima,et al.  The Mechanism of a Defective IFN-γ Response to Bacterial Toxins in an Atopic Dermatitis Model, NC/Nga Mice, and the Therapeutic Effect of IFN-γ, IL-12, or IL-18 on Dermatitis1 , 2001, The Journal of Immunology.

[22]  G. Tiegs,et al.  Inducible nitric oxide synthase is critical for immune-mediated liver injury in mice. , 2001, The Journal of clinical investigation.

[23]  L. Moldawer,et al.  Reduced Susceptibility of Nonobese Diabetic Mice to TNF-α and d-Galactosamine-Mediated Hepatocellular Apoptosis and Lethality1 , 2000, The Journal of Immunology.

[24]  N. Koide,et al.  Augmentation of Nitric Oxide Production by Gamma Interferon in a Mouse Vascular Endothelial Cell Line and Its Modulation by Tumor Necrosis Factor Alpha and Lipopolysaccharide , 2000, Infection and Immunity.

[25]  N. Koide,et al.  Expression of Fas and Fas Ligand on Mouse Renal Tubular Epithelial Cells in the Generalized Shwartzman Reaction and Its Relationship to Apoptosis , 1999, Infection and Immunity.

[26]  N. Koide,et al.  Role of Nitric Oxide in Lipopolysaccharide-Induced Hepatic Injury in d-Galactosamine-Sensitized Mice as an Experimental Endotoxic Shock Model , 1999, Infection and Immunity.

[27]  H. Sato,et al.  IgE hyperproduction through enhanced tyrosine phosphorylation of Janus kinase 3 in NC/Nga mice, a model for human atopic dermatitis. , 1999, Journal of immunology.

[28]  N. Koide,et al.  Apoptotic cell death in the response of D-galactosamine-sensitized mice to lipopolysaccharide as an experimental endotoxic shock model , 1996, Infection and immunity.

[29]  G. Trinchieri,et al.  Interleukin 12, interferon gamma, and tumor necrosis factor alpha are the key cytokines of the generalized Shwartzman reaction , 1994, The Journal of experimental medicine.

[30]  M. Leist,et al.  Murine hepatocyte apoptosis induced in vitro and in vivo by TNF-alpha requires transcriptional arrest. , 1994, Journal of immunology.

[31]  B. Ryffel,et al.  Interferon gamma receptor deficient mice are resistant to endotoxic shock , 1994, The Journal of experimental medicine.

[32]  A. Billiau,et al.  Interferon gamma, a mediator of lethal lipopolysaccharide-induced Shwartzman-like shock reactions in mice , 1990, The Journal of experimental medicine.

[33]  S. Tannenbaum,et al.  Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. , 1982, Analytical biochemistry.