title: Liver Injury After Invariant NKT Cell Activation by Free Alpha-galactosylceramide and Alpha-galactosylceramide-loaded Dendritic Cells.
abstract: OBJECTIVE
  Both free alpha-galactosylceramide (αGalCer) and αGalCer-loaded dendritic cells (DCG) activate invariant natural killer T (iNKT) cells to varying degrees, with αGalCer inducing liver injury. We sought to evaluate liver injury by these two pathways.
  
  
  METHODS
  Mice were injected with αGalCer or DCG followed by analysis of serum alanine transaminase (ALT) activity levels, mortality and liver function.
  
  
  RESULTS
  While ALT levels were elevated after DCG in a tumor necrosis factor (TNF)-α-dependent manner, DCG did not cause lethal injury. More serious injury of liver CD31-positive endothelial cells (CD31(+) EC) was observed in mice treated with αGalCer than with DCG. Furthermore, liver CD31(+) EC of αGalCer-treated mice induced naïve liver lymphocytes to produce TNF-α.
  
  
  CONCLUSIONS
  DCG treatment did not induce lethal liver injury. CD31(+) EC may play an antigen-presenting role to iNKT cells after αGalCer treatment and may be a cause of lethal injury.
authors.affiliation: Department of Surgery, Division of Gastrointestinal Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hasegawa
authors.affiliation: Department of Surgery, Division of Gastrointestinal Surgery, Kobe University Graduate School of Medicine, Kobe, Japan kiyama@med.kobe-u.ac.jp.
authors.forename: Kimihiro
authors.initials: K
authors.lastname: Yamashita
authors.affiliation: Department of Surgery, Division of Gastrointestinal Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Otsubo
authors.affiliation: Department of Surgery, Division of Gastrointestinal Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kakeji
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis; D003713:Dendritic Cells / Q000187:drug effects / Q000637:transplantation*; D005260:Female; D005699:Galactosylceramides / Q000494:pharmacology*; D022781:Hepatocytes / Q000502:physiology; D007167:Immunotherapy; D008099:Liver / Q000473:pathology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D005699:Galactosylceramides; D014409:Tumor Necrosis Factor-alpha; C493154:alpha-galactosylceramide; D000410:Alanine Transaminase
keywords: NKT cells; endothelial cells; immunotherapy; liver injury