Fas-mediated apoptosis of peripheral blood mononuclear cells in patients with hepatitis C.
In the present study, we demonstrated that a close relationship exists between hepatitis C virus (HCV) infection of peripheral blood mononuclear cells (PBMCs) and cell-surface Fas expression in patients with hepatitis C, and showed the possibility of PBMCs apoptosis via a Fas-mediated system. The expression of Fas on PBMCs was found by flowcytometric analysis to be significantly increased in these patients. In addition, the treatment of patients' PBMCs with anti-Fas antibody induced cell death, with nuclear condensation and fragmentation and cellular DNA fragmentation. These data indicate that the patients' PBMCs expressed a large amount of functional Fas on the cell surface and were susceptible to stimulation against Fas, causing apoptotic cell death. We then quantified the serum-soluble Fas ligand (sFasL), which was known to bind to Fas and induce the apoptotic signals into the sensitized cells. The patients' serum sFasL levels were significantly higher than those of normal subjects and showed a good negative correlation with their PBMC number. To demonstrate the correlation between Fas expression and HCV infection, nested reverse transcriptase polymerase chain reaction (RT-PCR) was performed to detect HCV RNA. Interestingly, HCV RNA was preferentially detected from Fas-positive cells but not from Fas-negative cells, which had been isolated from PBMCs by magnetic beads. These results suggest that HCV infection of PBMCs might induce Fas expression and additional stimulation such as sFasL might induce apoptosis in these Fas-expressing cells. These mechanisms, in addition to hypersplenism, may explain the decrease in the number of PBMCs observed in patients with chronic hepatitis C.
The Third Department of Internal Medicine, Asahikawa Medical College, Hokkaido, Japan.
N
N
Taya
Y
Y
Torimoto
M
M
Shindo
K
K
Hirai
C
C
Hasebe
Y
Y
Kohgo
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis; D002470:Cell Survival / Q000187:drug effects; D004912:Erythrocytes / Q000378:metabolism* / Q000821:virology; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D012367:RNA, Viral; D019014:fas Receptor