PMID- 15906084
OWN - NLM
STAT- MEDLINE
DCOM- 20050927
LR  - 20181113
IS  - 0945-6317 (Print)
IS  - 0945-6317 (Linking)
VI  - 446
IP  - 6
DP  - 2005 Jun
TI  - A murine model of NKT cell-mediated liver injury induced by 
      alpha-galactosylceramide/d-galactosamine.
PG  - 663-73
AB  - Natural killer-T (NKT) cells are rich in the liver. However, their involvement in 
      liver injury is not fully understood. We developed here a new murine model of 
      NKT-cell-activation-associated liver injury, and investigated a role of tumor 
      necrosis factor alpha (TNF-alpha) and Fas in pathogenesis. We injected 
      intraperitoneally alpha-galactosylceramide (alpha-GalCer), an NKT-cell stimulant, 
      into D-galactosamine (GalN)-sensitized mice. Survival rate, pathological changes 
      of the liver, and plasma concentrations of cytokines were studied. 
      Alpha-GalCer/GalN administration gave a lethal effect within 7 h, making 
      pathological changes such as massive parenchymal hemorrhage, hepatocyte 
      apoptosis, sinusoidal endothelial cell injury, and close apposition of 
      lymphocytes to apoptotic hepatocytes. Anti-NK1.1 mAb-pretreated mice and 
      Valpha14NKT knock out (KO) mice did not develop liver injury. Tumor necrosis 
      factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were elevated at 4 h in 
      the plasma. These cytokines were produced by hepatic lymphocytes as demonstrated 
      by in vitro stimulation with alpha-GalCer. The lethal effect was suppressed in 
      TNF-alpha KO mice, TNF receptor-1 KO mice, and lpr/lpr (Fas deficient) mice, 
      whereas it was not in IFN-gamma KO mice. These results indicate that the present 
      liver injury is characterized by parenchymal hemorrhage and hepatocyte apoptosis, 
      and mediated by TNF-alpha secretion and direct cytotoxicity of 
      alpha-GalCer-activated NKT cells.
FAU - Fujii, Hideki
AU  - Fujii H
AD  - Department of Hepatology, Osaka City University Graduate School of Medicine, 
      1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan. rolahidek@med.osaka-cu.ac.jp
FAU - Seki, Shuichi
AU  - Seki S
FAU - Kobayashi, Sawako
AU  - Kobayashi S
FAU - Kitada, Takuya
AU  - Kitada T
FAU - Kawakita, Nobuyoshi
AU  - Kawakita N
FAU - Adachi, Keishi
AU  - Adachi K
FAU - Tsutsui, Hiroko
AU  - Tsutsui H
FAU - Nakanishi, Kenji
AU  - Nakanishi K
FAU - Fujiwara, Hiromi
AU  - Fujiwara H
FAU - Ikarashi, Yoshinori
AU  - Ikarashi Y
FAU - Taniguchi, Masaru
AU  - Taniguchi M
FAU - Kronenberg, Mitchell
AU  - Kronenberg M
FAU - Ikemoto, Masaru
AU  - Ikemoto M
FAU - Nakajima, Yuji
AU  - Nakajima Y
FAU - Arakawa, Tetsuo
AU  - Arakawa T
FAU - Kaneda, Kenji
AU  - Kaneda K
LA  - eng
PT  - Journal Article
DEP - 20050520
PL  - Germany
TA  - Virchows Arch
JT  - Virchows Archiv : an international journal of pathology
JID - 9423843
RN  - 0 (Galactosylceramides)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (alpha-galactosylceramide)
RN  - 7535-00-4 (Galactosamine)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
EIN - Virchows Arch. 2006 Aug;449(2):279. Mitchell, Kronenberg [corrected to 
      Kronenberg, Mitchell]
MH  - Animals
MH  - Apoptosis/physiology
MH  - Chemical and Drug Induced Liver Injury
MH  - Disease Models, Animal
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Flow Cytometry
MH  - Galactosamine/pharmacology
MH  - Galactosylceramides/*toxicity
MH  - In Situ Nick-End Labeling
MH  - Interferon-gamma/blood/deficiency/genetics
MH  - Killer Cells, Natural/*immunology
MH  - Liver/*immunology/*injuries/pathology
MH  - Liver Diseases/*immunology/pathology
MH  - Mice
MH  - Mice, Knockout
MH  - Receptors, Tumor Necrosis Factor/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2005/05/21 09:00
MHDA- 2005/09/28 09:00
CRDT- 2005/05/21 09:00
PHST- 2004/11/08 00:00 [received]
PHST- 2005/03/25 00:00 [accepted]
PHST- 2005/05/21 09:00 [pubmed]
PHST- 2005/09/28 09:00 [medline]
PHST- 2005/05/21 09:00 [entrez]
AID - 10.1007/s00428-005-1265-8 [doi]
PST - ppublish
SO  - Virchows Arch. 2005 Jun;446(6):663-73. doi: 10.1007/s00428-005-1265-8. Epub 2005 
      May 20.