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.
Research Center for Infectious Disease, Aichi Medical University, Aichi, Japan. koide@aichi-med-u.ac.jp
Naoki
N
Koide
Akiko
A
Morikawa
Erdenezaya
E
Odkhuu
Abedul
A
Haque
Battuvshin
B
Badamtseren
Yoshikazu
Y
Naiki
Takayuki
T
Komatsu
Tomoaki
T
Yoshida
Takashi
T
Yokochi
D000818:Animals; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D019446:Endotoxemia / Q000276:immunology*; D005688:Galactosamine / Q000276:immunology*; D005690:Galactose / Q000008:administration & dosage / Q000031:analogs & derivatives; D005699:Galactosylceramides / Q000008:administration & dosage; D007155:Immunologic Factors / Q000008:administration & dosage; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008099:Liver / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism
D005699:Galactosylceramides; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D016693:Receptors, Antigen, T-Cell, alpha-beta; C493154:alpha-galactosylceramide; D009569:Nitric Oxide; D005688:Galactosamine; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; D053148:Caspase 3; D005690:Galactose