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PERIVASCULAR BRAIN MACROPHAGES ARE MAJOR TARGET OF SIV INFECTION

血管周围脑巨噬细胞是 SIV 感染的主要目标

基本信息

批准号：
6591311
负责人：
KENNETH C WILLIAMS
金额：
$ 11.11万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-05-01 至 2003-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6591311
关键词：
AIDS Mammalia communicable diseases immunology inflammation lymphatic system nervous system sexually transmitted diseases virus

项目摘要

The identification of distinct monocyte/macrophage populations that carry virus to the CNS and subsets within the CNS that are the target for infection by HIV/SIV is not defined In this study we have used immunohistochemistry and combined immunohistochemistry with in situ hybridization to define which populations of brain macrophages are infected at peak viremia and in SIVE Perivascular brain macrophages and the resident brain macrophage, microglia, are both CDllb and CD68 positive The perivascular macrophages, but not microglia, are also positive for CD14, CD45, and CD86 Multi-nucleated giant cells (MNGC), when present, are CD11b and CD68 positive like parenchymal microglia and perivascular macrophages The MNGC also are CD14 and CD45 positive, but express variable to non-detectable levels of CD4 Using combined immunohistochemistry and in situ hybridization and/or double label immunohistochemistry for myeloid cell markers followed by gp120, we demonstrat e th at the majority of gp120 or viral RNA positive cells are CD14 positive perivascular macrophages These perivascular cells are the major cell infected within the CNS during peak viremia (2 weeks post infection) and in animals with SIVE Less than 1% of the infected cells are resident microglia based upon immunohistochemistry These data underscore the importance of the perivascular macrophage as the major target of SIV in the CNS

不同单核细胞/巨噬细胞群体的鉴定携带病毒到中枢神经系统和中枢神经系统内的亚群， HIV/SIV感染的靶点尚未确定。采用免疫组化和免疫组化联合免疫组化方法，原位杂交来确定哪些脑巨噬细胞群在病毒血症高峰期感染，巨噬细胞和常驻脑巨噬细胞，小胶质细胞，都是 CD 11b和CD 68阳性血管周围巨噬细胞，但不小胶质细胞，也对CD 14，CD 45和CD 86多核巨细胞（MNGC），当存在时，是CD 11b和CD 68阳性样实质小胶质细胞和血管周围巨噬细胞MNGC也是 CD 14和CD 45阳性，但表达水平可变至不可检测水平免疫组化和原位杂交联合检测CD 4 和/或骨髓细胞标记物的双标记免疫组织化学其次是gp 120，我们在gp 120或病毒RNA阳性细胞是CD 14阳性血管周围巨噬细胞这些血管周围细胞是CNS内感染的主要细胞在病毒血症高峰期（感染后2周）和SIVE动物中不到1%的感染细胞是常驻小胶质细胞，这些数据强调了免疫组化的重要性。血管周围巨噬细胞是SIV在CNS中的主要靶点