Adenovirus-mediated Bcl-2 gene transfer inhibits apoptosis and promotes survival of allogeneic transplanted hepatocytes

被引:16
作者
Song, EW
Chen, JS
Antus, B
Su, FX
Wang, MH
Exton, MS
机构
[1] Sun Yat Sen Univ Med Sci, Sun Yat Sen Mem Hosp, Dept Hepatobiliary Surg, Guangzhou 510120, Peoples R China
[2] Univ Hosp Essen, Dept Nephrol, Essen, Germany
[3] Univ Hosp Essen, Dept Med Psychol, Essen, Germany
关键词
D O I
10.1067/msy.2001.116027
中图分类号
R61 [外科手术学];
学科分类号
摘要
Background. Donor hepatocyte apoptosis that is induced by host cytotoxic T lymphocytes (CTLs) limits the application of hepatocyte transplantation. Hepatocytes from Bcl-2 transgenic mi. ce can resist the lethal effect of anti-Fas antibody. However, the anti-apoptotic effect of Bcl-2 expression on allogeneic transplanted hepatocytes remains illusive. This study tested the feasibility of Bcl-2 gene transfer as an approach to inhibit CTL-mediated apoptosis in allogeneic transplanted hepatocytes. Methods. An adenovirus vector that encoded human Bcl-2 fe gene (AdCMVhBcl-2) was used to transfect cultured rat hepatocytes, which were then transplanted into allogeneic spleens. DNA fragmentation and caspase-3 activation were examined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling assay and immunohistochemistry for active caspase-3, respectively. Cocultivation of hepatocytes and allogeneic CD8(+) T lymphocytes was performed, and cytotoxicity on hepatocytes was examined by alanine transaminase release. Results. Bcl-2 gene transfer inhibited apoptosis and increased liver-associated enzyme activities in allogeneic transplanted hepatocytes, which were associated with inhibition of caspase-3 activation. Alanine transaminase release in hBcl-2 modified hepatocytes was lower compared with controls, which could not be further decreased by inhibition of Fas ligand and granzyme B. C onclusions. Adenovirus-mediated Bcl-2 gene transfer blocks CTL-mediated apoptosis in allogeneic hepatocytes by inhibition of caspase-3 activation. Bcl-2 gene transfer could be used to promote survival of transplanted hepatocytes.
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页码:502 / 511
页数:10
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