CD163, a marker of perivascular macrophages, is up-regulated by microglia in simian immunodeficiency virus encephalitis after haptoglobin-hemoglobin complex stimulation and is suggestive of breakdown of the blood-brain barrier
CD163, a marker of perivascular macrophages, is up-regulated by microglia in simian immunodeficiency virus encephalitis after haptoglobin-hemoglobin complex stimulation and is suggestive of breakdown of the blood-brain barrier
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DOI：
10.2353/ajpath.2008.070848
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发表时间：
2008-03-01
影响因子：
6
通讯作者：
Lackner, Andrew A.
中科院分区：
文献类型：
--
作者：
Borda, Juan T.;Alvarez, Xavier;Lackner, Andrew A.
巨噬细胞和小胶质细胞是中枢神经系统中人类免疫缺陷病毒和猿猴免疫缺陷病毒（SIV）感染的主要细胞类型。小胶质细胞可能在体内被感染，但缺乏广泛的生产性感染（即病毒 RNA 和蛋白质的存在）的证据。这一结论是有争议的，因为与淋巴细胞不同，巨噬细胞和小胶质细胞不能进行谨慎的免疫表型分析。在寻找其他单核细胞/巨噬细胞谱系细胞标记物中特别感兴趣的是 CD163；这种结合珠蛋白-血红蛋白 (Hp-Hb) 复合物的受体在红细胞溶解后在血浆中形成，仅在单核细胞/巨噬细胞谱系的细胞上表达。我们在患有或不患有脑炎的猕猴感染 SI[V 后的不同时间，通过多种技术在体外和体内检测了 CD163 的表达。在正常和急性SIV感染的动物中，以及在没有脑炎的SIV感染的动物中，在单核细胞/巨噬细胞谱系的细胞（包括血管周围巨噬细胞）中检测到CD163表达，但在实质小胶质细胞中没有检测到CD163表达。然而，在患有脑炎的慢性感染动物中，在存在 Hp-Hb 复合物的情况下，在 SIV 脑炎病变周围的活化小胶质细胞中检测到 CD163 表达，表明血脑屏障发生渗漏。在用 Hp-Hb 复合物刺激后，体外小胶质细胞上也诱导了 CD163 表达。我们得出结论，CD163 是正常猕猴和 SIV 感染早期阶段血管周围巨噬细胞的选择性标记物；然而，在感染脑炎的动物中，小胶质细胞也表达 CD163，这可能是由于血管受损而被激活。
Macrophages and microglia are the major cell types infected by human immunodeficiency virus and simian immunodeficiency virus (SIV) in the central nervous system. Microglia are likely infected in vivo, but evidence of widespread productive infection (ie, presence of viral RNA and protein) is lacking. This conclusion is controversial because, unlike lymphocytes, macrophages and microglia cannot be discreetly immunophenotyped. Of particular interest in the search for additional monocyte/macrophage-lineage cell markers is CD163; this receptor for haptoglobin-hemoglobin (Hp-Hb) complex, which forms in plasma following erythrolysis, is expressed exclusively on cells of monocyte/macrophage lineage. We examined CD163 expression in vitro and in vivo by multiple techniques and at varying times after SI[V infection in macaques with or without encephalitis. In normal and acutely SIV-infected animals, and in SIV-infected animals without encephalitis, CD163 expression was detected in cells of monocyte/macrophage lineage, including perivascular macrophages, but not in parenchymal microglia. However, in chronically infected animals with encephalitis, CD163 expression was detected in activated microglia surrounding SIV encephalitis lesions in the presence of Hp-Hb complex, suggesting leakage of the blood-brain barrier. CD163 expression was also induced on microglia in vitro after stimulation with Hp-Hb complex. We conclude that CD163 is a selective marker of perivascular macrophages in normal macaques and during the early phases of SIV infection; however, later in infection in animals with encephalitis, CD163 is also expressed by microglia, which are probably activated as a result of vascular Compromise.