HIV-1 induced destruction of neocortical extracellular matrix components in AIDS victims
HIV-1 induced destruction of neocortical extracellular matrix components in AIDS victims
复制标题
HIV-1 诱导的艾滋病患者新皮质细胞外基质成分的破坏
DOI：
10.1006/nbdi.1997.0143
复制
发表时间：
1997-01-01
影响因子：
6.1
通讯作者：
Celio, MR
中科院分区：
文献类型：
--
作者：
Belichenko, PV;Miklossy, J;Celio, MR
神经功能障碍在患有获得性免疫缺陷综合征（AIDS）的患者中并不少见，并且当表现出来时，暗示中枢神经系统的受累。在这里，人类免疫缺陷病毒（HIV）优先感染小胶质细胞，从而释放已知干扰神经元功能的物质。以这种方式释放的一类试剂是蛋白酶;这些蛋白酶降解细胞外基质（ECM）隔室中的某些组分，从而破坏其完整性，所述细胞外基质（ECM）隔室在细胞间通讯中起着至关重要的作用。我们希望确定是否ECM隔间确实是破坏了艾滋病患者的大脑。我们检查了27例艾滋病尸检病例的新皮层区域，其中包括9例诊断为艾滋病毒脑病（HIVE）的病例; 8例艾滋病毒血清阴性的各种类型的脑病变，包括病毒感染，也包括在这项研究中。通过免疫组织化学和原位杂交鉴定HIV抗原和DNA，通过凝集素染色和免疫组织化学鉴定ECM成分。在27例艾滋病病例中，9例HIVE患者中的每一个都完全没有标记的ECM成分; 18例无HIVE患者中的8例发生了大量损失，只有2例表现出正常的成分补充。在分层和地形变化方面，第II层和第III层受到的影响小于第V层至第VII层，额叶皮层相对于其他区域也是如此。这些发现证实了我们对HIV感染后大脑ECM降解的预期，这些变化很可能是艾滋病患者表现出的神经障碍的基础。(C)北京：科学出版社.
Neurological dysfunction is not uncommon in patients suffering from acquired immunodeficiency syndrome (AIDS) and, when manifested, intimates involvement of the central nervous system. Here, the human immunodeficiency virus (HIV) infects preferentially microglial cells, which thereby release substances known to interfere with neuronal function. One class of agents set free in this manner are proteases; these degrade certain components within, and thereby undermine the integrity of, the extracellular matrix (ECM) compartment, which plays a vital role in cell-to-cell communication. We wished to ascertain whether the ECM compartment is indeed disrupted in the brains of AIDS victims. We examined the neocortical areas of 27 AIDS autopsy cases, including 9 with diagnosed HIV-encephalopathy (HIVE); 8 HIV-seronegative cases with various types of brain lesion, including viral infections, were also included in this study. HIV-antigens and DNA were identified by use of immunohistochemistry and in situ hybridization, and ECM components by lectin staining and immunohistochemistry. Of the 27 AIDS cases examined, each of the 9 with HIVE was completely devoid of labeled ECM components; 8 of the 18 without HIVE had incurred substantial losses, and only 2 manifested a normal complement of constituents within this compartment With respect to stratal and topographic variations, layers II and III were less affected than layers V to VII, as was the frontal cortex relative to other areas. These findings confirmed our expectations of the brain's ECM undergoing degradation following HIV infection, and these changes may well underlie the neurological disturbances manifested in AIDS patients. (C) 1997 Academic Press.