Macrophage protection by addition of glutathione (GSH)-loaded erythrocytes to AZT and DDI in a murine AIDS model
Macrophage protection by addition of glutathione (GSH)-loaded erythrocytes to AZT and DDI in a murine AIDS model
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DOI：
10.1016/s0166-3542(02)00128-6
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发表时间：
2002-12-01
影响因子：
7.6
通讯作者：
Magnani, M
中科院分区：
文献类型：
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作者：
Fraternale, A;Casabianca, A;Magnani, M
单核巨噬细胞在HIV-1感染中起着核心作用，因为它们是第一批被感染的细胞之一，而且后来它们是病毒的重要宿主。因此，新设计的治疗方法应该考虑到这个细胞区室的保护。在此，我们报告了在小鼠艾滋病模型中获得的结果，通过添加AZT+DDI系统（gsh负载红细胞）能够保护巨噬细胞免受HIV-1感染。将5组lp - bm5感染小鼠分别给予AZT、DDI、两者联合、gsh负载红细胞、三者联合治疗。感染10周后，研究疾病参数，定量测定不同器官、骨髓和腹腔巨噬细胞中原病毒DNA的含量。结果表明，与AZT+DDI处理小鼠相比，AZT+DDI+ gsh负载红细胞处理小鼠的脑和骨髓巨噬细胞中前病毒DNA含量显著降低。这项研究可能有助于开发旨在阻断HIV-1在其体内储存库中的复制的策略。(C) 2002 Elsevier Science B.V.版权所有
Monocyte-macrophages play a central role in HIV-1 infection because they are among the first cells to be infected and because later they are important reservoirs for the virus. Thus, newly designed therapies should take into account the protection of this cell compartment. Herein, we report the results obtained in a murine AIDS model, by the addition to AZT+DDI of a system (GSH-loaded erythrocytes) able to protect macrophages against HIV-1 infection. Five groups of LP-BM5-infected mice were treated as follows: one group was treated by AZT, one group was treated by DDI, one group was treated by the combination of both, another by GSH-loaded erythrocytes, and finally, one by the combination of all three, After 10 weeks of infection the parameters of the disease were studied and the proviral DNA content in different organs and in macrophages of bone marrow and of the peritoneal cavity was quantified. The results obtained show that mice treated with AZT+DDI+GSH-loaded erythrocytes showed proviral DNA content in the brain and in macrophages of bone marrow that was significantly lower than in mice treated with AZT+DDI. This study may help developing strategies aimed at blocking HIV-1 replication in its reservoirs in the body. (C) 2002 Elsevier Science B.V. All rights reserved.