Blood-brain barrier disruption in simian immunodeficiency virus encephalitis
Blood-brain barrier disruption in simian immunodeficiency virus encephalitis
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DOI：
10.1046/j.1365-2990.2000.00275.x
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发表时间：
2000-10-01
影响因子：
5
通讯作者：
Hamilton, RL
中科院分区：
文献类型：
--
作者：
Luabeya, MK;Dallasta, LM;Hamilton, RL
感染的单核细胞源性巨噬细胞（MDM）被一些研究者认为在人类免疫缺陷病毒性脑炎（HIVE）的神经发病机制中起核心作用。最近提出，这些细胞通过破坏血脑屏障（BBB）紧密连接而进入中枢神经系统（CNS），这与活化的、HIV-1感染的、血管周围巨噬细胞的积累和血清蛋白外渗相关地发生在HIVE中（Am J Pathol 1999，155：1915-27）。本研究通过检查血管紧密连接相关蛋白、闭合蛋白和闭合小带-1（ZO-1）的免疫组化改变，在猴免疫缺陷病毒（SIV）感染的脑炎猕猴基底节组织中验证了这一假设。与未感染的猕猴和SIV感染的猕猴相比，SIVE猕猴的脑血管显示出碎片化和两种紧密连接蛋白的免疫反应性降低。这些变化与血管周围巨噬细胞的积累和异常的occludin和ZO-1免疫反应性在这些细胞内。此外，在血管紧密连接蛋白改变的区域观察到纤维蛋白原（一种血浆蛋白）的血管周围外渗，以及葡萄糖转运蛋白亚型-1（GLUT-1）（一种代谢性BBB标记物）从强线性染色模式向更不规则模式的变化。这些发现表明SIVE中紧密连接破坏与血管周围巨噬细胞积聚相关。虽然从这些研究中无法确定这种变化是否先于巨噬细胞浸润，或者继发于脑血管周围巨噬细胞的长期存在，但BBB完整性的破坏可能成为SIVE中血管周围巨噬细胞额外蓄积的门户。
Infected monocyte-derived macrophages (MDM) are thought by some investigators to play a central role in the neuropathogenesis of human immunodeficiency virus encephalitis (HIVE). It was recently proposed that these cells gain access to the central nervous system (CNS) through disruptions in blood-brain barrier (BBB) tight junctions, which occur in HIVE in association with accumulation of activated, HIV-1-infected, perivascular macrophages and serum protein extravasation (Am J Pathol 1999, 155: 1915-27). The present study tested this hypothesis in basal ganglia tissue from simian immunodeficiency virus (SIV)-infected macaques with encephalitis by examining vessels for immunohistochemical alterations in the tight junction-associated proteins, occludin and zonula occludens-1 (ZO-1). Compared to non-infected macaques and SIV-infected macaques without encephalitis, cerebral vessels from macaques with SIVE showed fragmentation and decreased immunoreactivity for both tight junction proteins. These alterations were associated with accumulation of perivascular macrophages and aberrant occludin and ZO-1 immunoreactivity within these cells. In addition, perivascular extravasation of fibrinogen, a plasma protein, and a change from a strong linear staining pattern to a more irregular pattern of glucose transporter isoform-1 (GLUT-1), a metabolic BBB marker, were observed in regions with vascular tight junction protein alterations. These findings demonstrate that tight junction disruption occurs in SIVE in association with perivascular macrophage accumulation. While it cannot be ascertained from these studies whether such changes precede macrophage infiltration, or are secondary to the chronic presence of macrophages around cerebral vessels, disruptions in BBB integrity could serve as portals for additional accumulation of perivascular macrophages in SIVE.