Lethal toxicity, severe endothelial injury, and a threshold effect with high doses of an adenoviral vector in baboons
Lethal toxicity, severe endothelial injury, and a threshold effect with high doses of an adenoviral vector in baboons
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DOI：
10.1089/10430340152712692
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发表时间：
2002-01-01
影响因子：
4.2
通讯作者：
Langston, C
中科院分区：
文献类型：
--
作者：
Morral, N;O'Neal, WK;Langston, C
在两只接受高剂量或低剂量载体（分别为1.2 x 10（13）或1.2 x 10（12）颗粒/kg）的狒狒中比较了静脉注射表达β-半乳糖苷酶的第一代腺病毒载体的效果。高剂量狒狒出现急性症状，血小板计数降低，肝酶升高，并在注射后48小时濒死，而低剂量狒狒未出现症状。在高剂量狒狒的肝脏、脾脏和动脉血管内皮中，β-半乳糖苷酶转基因的表达显著，但在低剂量狒狒中，β-半乳糖苷酶转基因的表达更为有限，并保留了内皮。血管内皮损伤是高剂量狒狒中最显著的异常。广泛的组织学研究提供了灵长类动物中与致死剂量的第一代腺病毒载体相关的病理学的详细图片。
The effects of intravenous administration of a first-generation adenoviral vector expressing beta-galactosidase were compared in two baboons receiving a high dose or lower dose of vector, 1.2 x 10(13) or 1.2 x 10(12) particles/kg, respectively. The high-dose baboon developed acute symptoms, decreased platelet counts, and increased liver enzymes, and became moribund at 48 hr after injection, while the lower-dose baboon developed no symptoms. Expression of the beta-galactosidase transgene was prominent in liver, spleen, and endothelium of the arterial vasculature in the high-dose baboon, but was much more limited and spared the endothelium in the lower-dose baboon. Injury to the vascular endothelium was the most prominent abnormality in the high-dose baboon. Extensive histological studies provide a detailed picture of the pathology associated with a lethal dose of first-generation adenoviral vector in a primate.