REQUIREMENT FOR MACROPHAGES IN NEURONAL INJURY INDUCED BY HIV ENVELOPE PROTEIN GP120
REQUIREMENT FOR MACROPHAGES IN NEURONAL INJURY INDUCED BY HIV ENVELOPE PROTEIN GP120
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DOI：
10.1097/00001756-199210000-00023
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发表时间：
1992-10-01
期刊：
影响因子：
1.7
通讯作者：
LIPTON, SA
中科院分区：
文献类型：
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作者：
LIPTON, SA
HIV-1相关的神经元损伤可能涉及病毒蛋白和细胞因子的复杂网络，但神经元本身不受感染。研究表明，HIV包膜蛋白gp 120会导致神经元游离钙早期增加，随后出现延迟的兴奋性毒性损伤，而N-甲基-D-天冬氨酸（NMDA）拮抗剂可以预防这种损伤。在本研究中，我们发现gp 120对视网膜神经节细胞神经元的损伤作用需要在出生后视网膜的神经胶质细胞混合培养物中存在巨噬细胞。在培养的24小时内，20 pM gp 120损伤了含有巨噬细胞和其他神经胶质细胞的培养物中近40%的视网膜神经节细胞，而在耗尽巨噬细胞的培养物中，没有发现gp 120对视网膜神经节细胞的有害作用。因此，gp 120对神经元的毒性作用似乎是间接的，通过激活巨噬细胞和其他胶质细胞介导。
HIV-1-RELATED neuronal injury may involve a complex web of viral proteins and cytokines, but neurons themselves are not infected. The HIV envelope protein gp120 has been shown to engender an early increase in neuronal free calcium followed by delayed excitotoxic-like damage, which is prevented by N-methyl-D-aspartate (NMDA) antagonists. In the present study, we found that the injurious effects of gp120 on retinal ganglion cell neurons require the presence of macrophages in mixed neuronalglial cultures of postnatal retina. Within 24 hours of incubation, 20 pM gp120 injured nearly 40% of retinal ganglion cells in cultures containing macrophages and other glial cells, whereas no deleterious effects of gp120 were noted on retinal ganglion cells in cultures depleted of macrophages. Thus, the toxic effect of gp120 on neurons appears to be an indirect one, mediated by activation of macrophages and perhaps other glial cells.