Singh Kumud K, Nathamu Satyanarayana, Adame Anthony, Alire Tara U, Dumaop Wilmar, Gouaux Ben, Moore David J, Masliah Eliezer
Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.
Neurobehav HIV Med. 2011 May 1;3:41-52. doi: 10.2147/NBHIV.S19969.
Mannose binding lectin (MBL) activates complement pathway that leads to pathogen opsonization and phagocytosis. MBL deficiency is linked to HIV transmission and disease progression. We sought to determine the role of MBL in HIV encephalitis (HIVE) by evaluating its presence and distribution in the HIV-1-infected brain and by assessing its association with monocyte chemoattractant protein-1 (MCP-1) expression. This retrospective study utilized archived post-mortem brain tissues obtained from 35 individuals enrolled in a longitudinal study as part of the California NeuroAIDS Tissue Network. MBL, MCP-1 and brain cell markers in post-mortem brain tissues with or without HIVE were evaluated using immunocytochemistry, immunofluorescence, confocal microscopy, and western blots. MBL was expressed in neurons, astrocytes, microglia, and oligodendrocytes of the frontal cortex of the HIV-1-infected brain. Overall, there were 30% to 40% more MBL-positive brain cells in HIVE vs non-HIVE cases (P = 0.01, paired t-test). Specifically, there was an increased MBL expression in the neuronal axons of HIVE cases. Also, western blots showed 3- to 4-fold higher levels of 78 kD MBL trimers in HIVE vs non-HIVE cases. This MBL-HIVE link was further confirmed by MBL associated higher MCP-1 expression in HIVE vs non-HIVE cases. HIV negative healthy individuals and normal or the gp120 transgenic mice did not show any differential MBL expression. Increased MBL expression in the major brain cell types, specifically in the neuronal axons of HIVE brain, and MBL associated higher MCP-1 expression in HIVE suggest that MBL could cause neuroinflammation and neuronal injury through MBL complement activation pathway.
甘露糖结合凝集素（MBL）激活补体途径，导致病原体调理吞噬作用。MBL缺乏与HIV传播和疾病进展有关。我们试图通过评估其在HIV-1感染大脑中的存在和分布，以及评估其与单核细胞趋化蛋白-1（MCP-1）表达的关联，来确定MBL在HIV脑炎（HIVE）中的作用。这项回顾性研究利用了从35名参与纵向研究的个体中获得的存档尸检脑组织，该纵向研究是加利福尼亚神经艾滋病组织网络的一部分。使用免疫细胞化学、免疫荧光、共聚焦显微镜和蛋白质印迹法评估有或没有HIVE的尸检脑组织中的MBL、MCP-1和脑细胞标志物。MBL在HIV-1感染大脑额叶皮质的神经元、星形胶质细胞、小胶质细胞和少突胶质细胞中表达。总体而言，与非HIVE病例相比，HIVE病例中MBL阳性脑细胞多30%至40%（配对t检验，P = 0.01）。具体而言，HIVE病例的神经元轴突中MBL表达增加。此外，蛋白质印迹显示，与非HIVE病例相比，HIVE病例中78 kD MBL三聚体水平高3至4倍。HIVE病例中MBL与较高的MCP-1表达相关，进一步证实了这种MBL与HIVE的联系。HIV阴性健康个体以及正常或gp120转基因小鼠未显示出任何MBL表达差异。主要脑细胞类型中MBL表达增加，特别是在HIVE大脑的神经元轴突中，以及HIVE中MBL与较高的MCP-1表达相关，表明MBL可能通过MBL补体激活途径导致神经炎症和神经元损伤。
