Fas ligand gene transfer to the vessel wall inhibits neointima formation and overrides the adenovirus-mediated T cell response.
Fas ligand gene transfer to the vessel wall inhibits neointima formation and overrides the adenovirus-mediated T cell response.
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DOI：
10.1073/pnas.95.3.1213
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发表时间：
1998-02
影响因子：
11.1
通讯作者：
M. Sata;H. Perlman;D. Muruve;Marcy Silver;M. Ikebe;T. Libermann;P. Oettgen;K. Walsh;K. Walsh
中科院分区：
文献类型：
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作者：
M. Sata;H. Perlman;D. Muruve;Marcy Silver;M. Ikebe;T. Libermann;P. Oettgen;K. Walsh;K. Walsh
血管平滑肌细胞（VSMC）对损伤的反应性增殖在血管疾病的发病机制中起着关键作用。Fas配体（FasL）诱导Fas携带细胞凋亡，其在活化T细胞上的表达有助于调节免疫应答和生理性细胞更新。在这里，我们表明，复制缺陷型腺病毒编码FasL（Ad-FasL）诱导Fas轴承VSMCs的凋亡。当引入局部球囊损伤的大鼠颈动脉，一个良好的表征模型的VSMC衍生病变，Ad-FasL作为一个有效的抑制剂的新生内膜形成。在用空腺病毒载体免疫的大鼠中，在局部递送表达β-半乳糖苷酶的病毒（Ad-betagal）后检测到血管壁的稳健的T细胞浸润，而在局部递送Ad-FasL后未检测到T细胞浸润。先前的免疫阻止了Ad-betagal的β-半乳糖苷酶表达，而FasL转基因的表达不受影响。当Ad-betagal和Ad-FasL一起递送给预免疫动物时，T细胞浸润减少，β-半乳糖苷酶表达恢复。这些数据表明，Fas配体基因转移可以有效地抑制损伤诱导的血管病变的形成，并可以允许腺病毒携带的细胞逃避免疫破坏。
Proliferation of vascular smooth muscle cells (VSMCs) in response to injury plays a key role in the pathogenesis of vascular disorders. Fas ligand (FasL) induces apoptosis in Fas-bearing cells, and its expression on activated T cells contributes to the regulation of the immune response and physiological cell turnover. Here, we show that a replication-defective adenovirus encoding FasL (Ad-FasL) induced apoptosis in Fas-bearing VSMCs. When introduced locally to balloon-injured rat carotid arteries, a well characterized model of a VSMC-derived lesion, Ad-FasL functioned as a potent inhibitor of neointima formation. In rats immunized with an empty adenoviral vector, robust T cell infiltration of the vessel wall was detected after local delivery of a beta-galactosidase-expressing virus (Ad-betagal), whereas T cell infiltrates were not detected after local delivery of Ad-FasL. Prior immunization prevented beta-galactosidase expression from Ad-betagal, whereas the expression of the FasL transgene was unaffected. When Ad-betagal and Ad-FasL were delivered together to preimmunized animals, T cell infiltration was reduced and beta-galactosidase expression was restored. These data demonstrate that Fas ligand gene transfer can effectively inhibit injury-induced vessel lesion formation and can allow adenovirus-harboring cells to evade immune destruction.