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<p>Sinusoidal obstruction syndrome (SOS) is a fatal liver condition resulting from sinusoidal endothelial cell injury and hepatocyte death, following liver or hematopoietic stem cell transplantation as well as chemotherapy. We showed evidence of platelet displacement and aggregation within the space of Disse in SOS. However, the relationship between platelets and hepatocyte death remains unclear. Using a mouse SOS model by intraperitoneal monocrotaline (270&#xa0;mg/kg; a pyrrolizidine alkaloide plant toxin) administration, we observed positive stains for terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and cleaved caspase-3, which are markers for apoptosis, in the liver by immunohistochemistry. At 48&#xa0;h of the SOS liver, aggregated platelets and hepatocytes around zone 3 were found to express Fas ligand (FasL) and Fas, respectively. Human peripheral blood platelets, when aggregated, could induce expression of FASL on themselves and then lead to apoptosis in co-cultured HepG2 cells. Treatment of recombinant soluble thrombomodulin (rTM), an anticoagulant and vascular endothelium-protective drug, prevented the hepatocyte death in the SOS mice. These findings suggest that the prevention of platelet aggregation is a potential therapeutic intervention against hepatocyte death and severe liver damage in SOS.</p>

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Platelet aggregation elicits FasL expression and hepatocyte apoptosis in sinusoidal obstruction syndrome

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月29日

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  • Yuri Higashi,
  • Seiichi Munesue,
  • Masakazu Saeki,
  • Ai Harashima,
  • Kumi Kimura,
  • Yu Oshima,
  • Ryohei Takei,
  • Satoshi Takada,
  • Shinichi Nakanuma,
  • Isamu Makino,
  • Tetsuo Ohta,
  • Shintaro Yagi,
  • Hidehiro Tajima,
  • Yasuhiko Yamamoto

摘要

Sinusoidal obstruction syndrome (SOS) is a fatal liver condition resulting from sinusoidal endothelial cell injury and hepatocyte death, following liver or hematopoietic stem cell transplantation as well as chemotherapy. We showed evidence of platelet displacement and aggregation within the space of Disse in SOS. However, the relationship between platelets and hepatocyte death remains unclear. Using a mouse SOS model by intraperitoneal monocrotaline (270 mg/kg; a pyrrolizidine alkaloide plant toxin) administration, we observed positive stains for terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and cleaved caspase-3, which are markers for apoptosis, in the liver by immunohistochemistry. At 48 h of the SOS liver, aggregated platelets and hepatocytes around zone 3 were found to express Fas ligand (FasL) and Fas, respectively. Human peripheral blood platelets, when aggregated, could induce expression of FASL on themselves and then lead to apoptosis in co-cultured HepG2 cells. Treatment of recombinant soluble thrombomodulin (rTM), an anticoagulant and vascular endothelium-protective drug, prevented the hepatocyte death in the SOS mice. These findings suggest that the prevention of platelet aggregation is a potential therapeutic intervention against hepatocyte death and severe liver damage in SOS.