ADENOVIRUS GENE-TRANSFER CAUSES INFLAMMATION IN THE BRAIN
ADENOVIRUS GENE-TRANSFER CAUSES INFLAMMATION IN THE BRAIN
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DOI：
10.1016/0306-4522(95)00068-t
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发表时间：
1995-06-01
期刊：
影响因子：
3.3
通讯作者：
CHARLTON, HM
中科院分区：
文献类型：
--
作者：
BYRNES, AP;RUSBY, JE;CHARLTON, HM
我们报告称，将 El 缺失的、非复制的人类 5 型腺病毒载体注射到大脑中会导致炎症反应。大部分炎症是由病毒颗粒本身直接诱导的，而不是通过载体表达新蛋白引起的。研究发现，炎症的严重程度取决于所用近交系大鼠的品系：PVG 大鼠对载体注射的反应比 AO 大鼠的炎症要少。将腺病毒载体注射到 AO 大鼠纹状体中 12 小时后，发现白细胞边缘化到附近血管壁。两天后，主要组织相容性复合物 I 类表达大幅增加，白细胞（主要是巨噬细胞和 T 细胞）大量浸润。腺病毒逆行转运至黑质神经元与该远处部位的延迟且不太强烈的炎症有关。尽管 AO 和 PVG 大鼠在长达六天的纹状体中表现出类似的反应，但后来 PVG 大鼠的炎症程度较轻。尽管存在炎症反应，但在注射后至少两个月内观察到标记蛋白β-半乳糖苷酶和腺病毒早期蛋白的载体驱动表达，尽管表达随着时间的推移而下降。在计划和解释使用这些载体的实验时，必须考虑腺病毒基因转移导致大脑炎症反应的观察结果。此外，我们得出的结论是，使用适当的大鼠品系可以减轻炎症的某些方面。
We report that injecting an El-deleted, non-replicating, human adenovirus type 5 vector into the brain leads to an inflammatory response. Much of this inflammation is induced directly by the virion particles themselves rather than through the expression of new proteins from the vector. The severity of inflammation was found to depend on the strain of inbred rat used: PVG rats have less inflammation than AO rats in response to a vector injection. Twelve hours after injection of adenovirus vectors into the striatum of AO rats, leukocytes were seen marginating to the walls of nearby blood vessels. By two days there was a large increase in major histocompatibility complex class I expression and a heavy infiltration of leukocytes, mainly macrophages and T cells. Retrograde transport of adenovirus to neurons of the substantia nigra was associated with a delayed and less intense inflammation at this distant site. Although AO and PVG rats showed comparable responses in the striatum up to six days, at later times PVG rats had less intense inflammation. In spite of the inflammatory response, vector-driven expression of the marker protein beta-galactosidase and an adenovirus early protein was seen for at least two months following the injection, although expression declined with time.The observation that adenovirus gene transfer leads to an inflammatory response in the brain must be taken into account when planning and interpreting experiments with these vectors. Furthermore, we conclude that using an appropriate strain of rat can diminish some aspects of the inflammation.