The size of sinusoidal fenestrae is a critical determinant of hepatocyte transduction after adenoviral gene transfer
The size of sinusoidal fenestrae is a critical determinant of hepatocyte transduction after adenoviral gene transfer
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DOI：
10.1038/sj.gt.3302326
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发表时间：
2004-10-01
期刊：
影响因子：
5.1
通讯作者：
De Geest, B
中科院分区：
文献类型：
--
作者：
Lievens, J;Snoeys, J;De Geest, B
腺病毒载体的亲肝性和肝内分布可能具有物种依赖性。在用含有肝细胞特异性α(1)-抗胰蛋白酶启动子驱动表达盒(AdAT(4))的E1E3E4缺失腺病毒载体转移后，在三种兔品系中评估肝细胞转导。静脉注射 4 x 10(12) 颗粒/kg 的 AdAT(4) 诱导荷兰贝尔特兔中的人类 apo A-I 水平高于 40 mg/dl，但在新西兰白兔和 Fauve de Bourgogne 兔中低于 1 mg/dl。荷兰带兔 (124 +/- 3.4 nm) 的正弦窗孔直径显着大于新西兰白兔 (108 +/- 1.3 nm) 和 Fauve de Bourgogne (105 +/- 2.6 nm) 兔，表明较小的尺寸构成了肝细胞转导的障碍。事实上，门静脉内转移之前先进行门静脉内注射癸酸钠，这将窦窗孔的直径增加至 123 +/- 3.4 nm（P
The hepatotropism and intrahepatic distribution of adenoviral vectors may be species dependent. Hepatocyte transduction was evaluated in three rabbit strains after transfer with E1E3E4-deleted adenoviral vectors containing a hepatocyte specific alpha(1)-antitrypsin promoter-driven expression cassette (AdAT(4)). Intravenous administration of 4 x 10(12) particles/kg of AdAT(4) induced human apo A-I levels above 40 mg/dl in Dutch Belt, but below 1 mg/dl in New Zealand White and Fauve de Bourgogne rabbits. Diameters of sinusoidal fenestrae were significantly ( P = 0.0014) larger in Dutch Belt (124 +/- 3.4 nm) than in New Zealand White (108 +/- 1.3 nm) and Fauve de Bourgogne (105 +/- 2.6 nm) rabbits, suggesting that a smaller size constitutes a barrier for hepatocyte transduction. Indeed, intraportal transfer preceded by intraportal injection of sodium decanoate, which increases the diameter of sinusoidal fenestrae to 123 +/- 3.4 nm ( P