Apoptosis

, Volume 13, Issue 8, pp 1013–1021

Blockade of the Fas/Fas ligand interaction suppresses hepatocyte apoptosis in ischemia-reperfusion rat liver

  • Hiroo Nakajima
  • Naruhiko Mizuta
  • Ikuya Fujiwara
  • Koichi Sakaguchi
  • Hiromitsu Ogata
  • Junji Magae
  • Hideo Yagita
  • Takehiko Koji
Original Paper

DOI: 10.1007/s10495-008-0234-5

Cite this article as:
Nakajima, H., Mizuta, N., Fujiwara, I. et al. Apoptosis (2008) 13: 1013. doi:10.1007/s10495-008-0234-5

Abstract

Hepatic ischemia-reperfusion injury remains a significant problem for liver surgery, including transplantation, and apoptosis has been implicated in this type of hepatic injury. Here we found that through the Fas/Fas ligand interaction apoptosis is involved in the late phase of hepatic ischemia-reperfusion injury. The appearance of apoptotic hepatocytes increases significantly after reperfusion, reaching a maximum 12 h after reperfusion. The transcription levels of Fas and Fas ligand are increased after reperfusion. Fas is expressed on hepatocytes, while Fas ligand is expressed on infiltrating immune cells. A close spatial and temporal association of Fas expression and apoptotic cells is demonstrated in the histological observation. These results suggest that infiltrating cells induce apoptosis of hepatocytes through the Fas/Fas ligand interaction, leading to hepatocyte injury. Furthermore, an injection of anti-Fas antibody or neutralizing anti-Fas ligand antibody results in a dramatic decrease in the occurrence of hepatocyte apoptosis and hepatic infiltration of macrophages and natural killer cells as well as liver injury. Our results suggest that blockage of the Fas/Fas ligand interaction is a promising strategy for suppression of hepatic ischemia-reperfusion injury.

Keywords

Hepatocyte Ischemia-reperfusion Apoptosis Fas Fas ligand 

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Hiroo Nakajima
    • 1
  • Naruhiko Mizuta
    • 1
  • Ikuya Fujiwara
    • 1
  • Koichi Sakaguchi
    • 1
  • Hiromitsu Ogata
    • 2
  • Junji Magae
    • 3
  • Hideo Yagita
    • 4
  • Takehiko Koji
    • 5
  1. 1.Department of Endocrine, Breast SurgeryKyoto Prefectural University of MedicineKyotoJapan
  2. 2.National Institute of Public HealthSaitamaJapan
  3. 3.Radiation Safety Research Center, Nuclear Technology Research LaboratoryCentral Research Institute of Electric Power IndustryTokyoJapan
  4. 4.Department of ImmunologyJuntendo University School of MedicineTokyoJapan
  5. 5.Department of Histology and Cell BiologyNagasaki University School of MedicineNagasakiJapan