CD163, A MARKER OF PERIVASCULAR MACROPHAGES IS UPREGULATED ON MICROGLIA IN SIVE

CD163（一种血管周围巨噬细胞的标记物）在 SIVE 中的小胶质细胞上表达上调

• 批准号: 7562374
• 负责人: JUAN BORDA
• 金额: $ 7.16万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7562374
• 关键词: Acquired Immunodeficiency Syndrome; Animals; Blood - brain barrier anatomy; Blood Vessels; Brain; Cell Surface Receptors; Cells; Cellular Morphology; Complex; Computer Retrieval of Information on Scientific Projects Database; Cysteine-Rich Domain; Data; Encephalitis; Family; Funding; Grant; HIV; HLA-DR Antigens; Haptoglobins; Hemoglobin; Homeostasis; Human; In Vitro; Infection; Institution; Label; Lesion; Macaca; Macaca mulatta; Microglia; Minor; Neuraxis; Phase; Polymerase Chain Reaction; RNA; Research; Research Personnel; Resources; SIV; Source; Techniques; Time; Tissues; United States National Institutes of Health; Up-Regulation; cell type; haptoglobin-hemoglobin complex; hemoglobin-haptoglobin receptor; in vivo; macrophage; member; monocyte; scavenger receptor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Macrophages and microglia are the major cell types infected in the central nervous system of humans infected with HIV and macaques infected with SIV. Microglia are the resident macrophages of the brain and have been shown to be quite sensitive to even minor disturbances of central nervous system (CNS) homeostasis, and are readily activated. Activation of microglia induces changes in cellular morphology and in the expression of cell surface receptors. CD163 is a member of the scavenger receptor family with cysteine-rich domains (SCRC) identified as a receptor of haptoglobin-hemoglobin (Hp-Hb) complex and exclusively expressed by cells of monocyte-macrophage lineage. We examined the expression of CD163 in vitro and in vivo by multiple techniques and at varying times after SIV infection in animals with or without SIVE. Our data show that CD163 is expressed by cells of monocyte/macrophage lineage including perivascular macrophages but not parenchymal microglia in normal and acutely SIV-infected animals or animals with terminal AIDS without encephalitis. CD163 expression was detected in activated microglia (HLA-DR+) surrounding SIVE lesions in chronically infected macaques with severe encephalitis in the presence of haptoglobin-haemoglobin complex (Hp-Hb) in the tissue suggesting breakdown of the blood-brain-barrier. CD163 expression was also induced in microglia in vitro by stimulation with Hp-Hb complex indicating that the interaction of the Hp-Hb complex is required to trigger the upregulation of CD163. To confirm that activation of microglia was associated with the presence and upregulation of CD163 RNA we treated microglia isolated from rhesus macaque brain with Hp-Hb for 0, 6, 12, 18 and 48 h and performed quantitative real-time PCR. We observed a 2.5 fold increase of CD163 RNA in the microglia treated with haptoglobin-hemoglobin within 18hrs of exposure. We conclude that CD163 is a selective marker of perivascular macrophages in normal macaques and during the early phases of SIV infection. However, latter in infection CD163 also labels microglia that have been activated probably as a result of vascular compromise.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 巨噬细胞和小胶质细胞是感染HIV的人和感染SIV的猕猴中枢神经系统感染的主要细胞类型。小胶质细胞是大脑中驻留的巨噬细胞，已被证明对中枢神经系统(CNS)内环境平衡的微小干扰非常敏感，并且很容易被激活。小胶质细胞的激活会引起细胞形态和细胞表面受体表达的改变。CD163是清道夫受体家族的一员，其富含半胱氨酸结构域(SCRC)被鉴定为结合珠蛋白-血红蛋白(HP-Hb)复合体的受体，仅由单核巨噬细胞系的细胞表达。我们用多种技术检测了SIV感染后不同时间CD163在体内外的表达情况。我们的数据表明，在正常和急性SIV感染的动物或无脑炎的晚期艾滋病动物中，CD163在包括血管周围巨噬细胞在内的单核/巨噬细胞系细胞中表达，而在实质小胶质细胞中不表达。在慢性感染的重症脑炎猕猴的SIVE病变周围的激活的小胶质细胞(HLA-DR+)中检测到CD163的表达，该组织中存在结合珠蛋白-血红蛋白复合体(HP-Hb)，提示血脑屏障被破坏。Hp-Hb复合体在体外也能诱导小胶质细胞表达CD163，提示Hp-Hb复合体的相互作用是触发CD163表达上调的必要条件。为了证实小胶质细胞的激活与CD163RNA的存在和上调有关，我们用Hp-Hb处理恒河猴脑小胶质细胞0、6、12、18和48h，并进行实时定量PCR。我们观察到，在接触结合珠蛋白-血红蛋白的18小时内，小胶质细胞中CD163RNA的表达增加了2.5倍。我们认为CD163是正常猕猴和SIV感染早期血管周围巨噬细胞的选择性标记物。然而，感染后的CD163也标记了可能由于血管受损而被激活的小胶质细胞。