CNS invasion by CD14+/CD16+peripheral blood-derived monocytes in HIV dementia:: perivascular accumulation and reservoir of HIV infection
CNS invasion by CD14+/CD16+peripheral blood-derived monocytes in HIV dementia:: perivascular accumulation and reservoir of HIV infection
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DOI：
10.1080/135502801753248114
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发表时间：
2001-12-01
影响因子：
3.2
通讯作者：
Rappaport, J
中科院分区：
文献类型：
--
作者：
Fischer-Smith, T;Croul, S;Rappaport, J
CD14+/CD16+单核细胞增多与HIV痴呆有关；这些细胞进入中枢神经系统被认为在HIV诱导的神经系统疾病的发病机制中起重要作用。这一模型表明，中枢神经系统外的事件导致单核细胞激活，启动了导致艾滋病毒痴呆的过程。为了研究这种激活的单核细胞亚群在HIV痴呆发病机制中的作用，我们检查了HIV脑病(HIVE)患者、无脑病的HIV患者和血清阴性对照的脑标本。蜂窝内可见血管周围巨噬细胞聚集。在小胶质细胞结节和血管周围浸润液中发现的这些细胞大多是CD14+/CD16+。P24抗原与CD14和CD16共存，提示CD14+/CD16+巨噬细胞是HIV-1感染中枢神经系统的主要宿主。CD45/LCA染色可区分血管周围巨噬细胞和常驻小胶质细胞。除血管周围和结节外，CD16还在整个白质内染色分支细胞。这些细胞比白质中CD14阳性的细胞分支更多、更丰富。P24和CD16的双重染色表明，这些细胞经常感染艾滋病毒-1。蜂窝中CD14+细胞的显著分布促使我们对脑脊液中可溶性CD14水平进行了分析。在中重度HIV痴呆患者中观察到较高水平的可溶性CD14(SCD14)，提示sCD14可作为替代标记物。CD14+/CD16+单核细胞可能在其他神经系统疾病中发挥作用，sCD14可能有助于评估这些疾病。
Increases in circulating CD14+/CD16+ monocytes have been associated with HIV dementia; trafficking of these cells into the CNS has been proposed to play an important role in the pathogenesis of HIV-induced neurological disorders. This model suggests that events outside the CNS leading to monocyte activation initiate the process leading to HIV dementia. To investigate the role of this activated monocyte subset in the pathogenesis of HIV dementia, we examined brain specimens from patients with HIV encephalopathy (HIVE), HIV without encephalopathy, and seronegative controls. An accumulation of perivascular macrophages was observed in HIVE. The majority of these cells identified in microglial nodules and in the perivascular infiltrate were CD14+/CD16+. P24 antigen colocalized with both CD14 and CD16 suggesting that the CD14+/CD16+ macrophage is a major reservoir of HIV-1 infection in CNS. Using CD45/LCA staining, the perivascular macrophage was distinguished from resident microglia. In addition to perivascular and nodular localizations, CD16 also stained ramified cells throughout the white matter. These cells were more ramified and abundant than cells positive for CD14 in white matter. Double staining for p24 and CD16 suggests that these cells were often infected with HIV-1. The prominent distribution of CD14+ cells in HIVE prompted our analysis of soluble CD14 levels in cerebrospinal fluid. Higher levels of soluble CD14 (sCD14) were observed in patients with moderate-to-severe HIV dementia, suggesting the utility of sCD14 as a surrogate marker. CD14+/CD16+ monocytes may play a role in other neurological disorders and sCD14 may be useful for evaluating these conditions.