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

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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.

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Authors and Affiliations

  1. Department of Endocrine, Breast Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Hiroo Nakajima, Naruhiko Mizuta, Ikuya Fujiwara & Koichi Sakaguchi

  2. National Institute of Public Health, Saitama, Japan

    Hiromitsu Ogata

  3. Radiation Safety Research Center, Nuclear Technology Research Laboratory, Central Research Institute of Electric Power Industry, 2-11-1 Iwado Kita, Komae-shi, Tokyo, 201-8511, Japan

    Junji Magae

  4. Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan

    Hideo Yagita

  5. Department of Histology and Cell Biology, Nagasaki University School of Medicine, Nagasaki, Japan

    Takehiko Koji

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  1. Hiroo Nakajima
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  2. Naruhiko Mizuta
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  3. Ikuya Fujiwara
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  4. Koichi Sakaguchi
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  5. Hiromitsu Ogata
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Correspondence to Junji Magae.

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Nakajima, H., Mizuta, N., Fujiwara, I. et al. Blockade of the Fas/Fas ligand interaction suppresses hepatocyte apoptosis in ischemia-reperfusion rat liver. Apoptosis 13, 1013–1021 (2008). https://doi.org/10.1007/s10495-008-0234-5

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