Significance of Fas antigen-mediated apoptosis in human fulminant hepatic failure.
OBJECTIVE
The aim of this study was to elucidate the role of apoptosis in human fulminant hepatic failure. We studied the expression of Fas antigen on liver tissues, Fas ligand in lymphocytes, and soluble Fas ligand in patients' serum.


METHODS
On finding apoptotic cells in fulminant hepatic failure liver, we first examined them using the TUNEL method. Subsequently, the expression of Fas was studied by immunostaining. Simultaneously, Fas ligand presenting on both liver-infiltrated cells and peripheral lymphocytes was studied by reverse transcription-polymerase chain reaction, and soluble Fas ligand in sera was measured by ELISA.


RESULTS
By using the TUNEL method, we first demonstrated that many apoptotic cells existed in fulminant hepatic failure but not in normal ones. Our immunohistochemistry study showed that many hepatocytes in fulminant hepatic failure strongly expressed Fas. In addition, Fas ligand on both liver-infiltrating lymphocytes and peripheral lymphocytes in fulminant hepatic failure patients was detected. The serum level of soluble Fas ligand was significantly increased in fulminant hepatic failure (mean value, 2.91 ng/ml in fulminant hepatic failure [n = 10], 1.62 ng/ml in acute hepatitis [n = 10], and 0.27 ng/ml in healthy controls [n = 10]). Furthermore, this serum level of sFas ligand was significantly associated with prothrombin time both in acute hepatitis and fulminant hepatic failure.


CONCLUSIONS
The present results indicate that Fas-mediated apoptosis may be one of the triggers for the induction of fulminant hepatic failure.
Ryo
K
K
Second Department of Pathology, Tokyo Women's Medical University, Japan.
Kamogawa
Y
Y
Ikeda
I
I
Yamauchi
K
K
Yonehara
S
S
Nagata
S
S
Hayashi
N
N
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D002648:Child; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000378:metabolism / Q000473:pathology; D017093:Liver Failure / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D012333:RNA, Messenger / Q000097:blood / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism / Q000502:physiology*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019014:fas Receptor