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

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.

Diverse Effects of FK506 on the Apoptosis of Hepatocytes and Infiltrating Lymphocytes in an Allografted Rat Liver

“…Accordingly, the allo-FK group showed a greater Bcl-2 expression in the pericaval hepatocytes than in the syn group on day 1 after OLT. As a result, FK was thus suggested to ameliorate the I/R injury after OLT via mediating the Bcl-2 expression on hapatocytes in zone Fas action (51,52). 2) Overexpression of Bcl-2 by gene transfer (47).…”

Hypoxia-Inducible Factor-2α Limits Natural Killer T Cell Cytotoxicity in Renal Ischemia/Reperfusion Injury

“…22 It was reported that blockade of the Fas/FasL interaction attenuated IRI both in the kidney 23 and in the liver. 24 So we isolated thymocytes, liver mononuclear cells (MNCs) and splenocytes, which were subjected to flow cytometry analyses. The results are summarized in Table 1, and a typical result is shown in Figure 1.…”

Mechanisms and Consequences of Ebolavirus-Induced Lymphocyte Apoptosis

“…However, apoptotic cell death of hepatocytes in EBOVinfected mice has not been reported. H&E and TUNEL staining in the liver have been used to study hepatocyte apoptosis in other models (26,27). We analyzed the livers of EBOV-infected mice to determine whether hepatocyte apoptosis was present.…”