Adenovirus-mediated expression of Fas ligand induces hepatic apoptosis after systemic administration and apoptosis of ex vivo-infected pancreatic islet allografts and isografts
Adenovirus-mediated expression of Fas ligand induces hepatic apoptosis after systemic administration and apoptosis of ex vivo-infected pancreatic islet allografts and isografts
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DOI：
10.1089/hum.1997.8.8-955
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发表时间：
1997-05-20
影响因子：
4.2
通讯作者：
Libermann, TA
中科院分区：
文献类型：
--
作者：
Muruve, DA;Nicolson, AG;Libermann, TA
Fas配体(Fas Ligand，FasL)介导Fas阳性细胞的凋亡，表达于少数组织，主要是活化的T淋巴细胞。我们构建了一种在巨细胞病毒(CMV)启动子控制下快速编码小鼠Fas的复制缺陷5型腺病毒(adCMV-FasL)。在体外，Jurkat细胞与感染AdCMV-FasL的COS细胞共同孵育时发生凋亡，全身注射AdCMV-FasL给Wistar大鼠或DBA/2J小鼠可在72小时内以剂量依赖的方式导致广泛的肝脏细胞凋亡和死亡，这一效应在LPR小鼠或同等剂量的AdCMV-beta Gal组动物中未见。小鼠胰岛在体外感染AdCMV-FasL后也发生了细胞凋亡，移植到同基因或异基因糖尿病受体体内后均出现原代无功能，这些结果表明AdCMV-FasL是研究Fas/FasL生物学的一种潜在的有用工具。
Fas ligand (FasL) mediates apoptosis of Fas-bearing cells and is expressed on a limited number of tissues, predominantly activated T lymphocytes, We describe the construction and biological activity of a replication-deficient type-5 adenovirus encoding murine Fast under the control of the cytomegalovirus (CMV) promoter (adCMV-FasL). In vitro, Jurkat cells undergo apoptosis when co-incubated with adCMV-FasL-infected COS cells, Systemic administration of adCMV-FasL to Wistar rats or DBA/2J mice results in widespread hepatic apoptosis and death in a dose-dependent manner within 72 hr, an effect not seen in lpr mice, or animals administered equivalent doses of adCMV-beta gal. Murine pancreatic islets also undergo apoptosis when infected ex vivo with adCMV-FasL, resulting in uniform primary nonfunction when transplanted into syngeneic or allogeneic diabetic recipients, These results indicate that adCMV-FasL is a potentially useful tool to study Fas/FasL biology.