人星形细胞HIV-1膜蛋白gp120新受体的免疫学鉴定

Identification a novel receptor on human astrocytes for HIV-1 envelope protein gp120 by immunological methods

自 1994年首次报导HIV 1外膜蛋白gp12 0与人胎儿星形细胞膜蛋白质位点 (推测分子量为 2 6 0kD ,命名为PAG)结合以来〔1〕,这项工作持续集中于研究该蛋白的功能与作用〔2〕。本研究藉助杂交瘤技术建立了一系列小鼠抗人星形细胞PAG)的单克隆抗体 ,这些抗体成功地抑制了 gp12 0与PAG的结合 ,抑制率可达 5 0 %以上 ;并几乎完全阻断了gp12 0介导的由摄入所致星形细胞内钙离子的升高。通过ELISA可证实抗体与星形细胞的特异反应 ;蛋白印迹和免疫沉淀试验结果表明PAG作为实体的存在。试验表明PAG对于 gp12 0与星形细胞的结合 ,对于gp12 0介导的星形细胞摄入所致钙离子的升高均有决定性作用。许多文献报导和研究表明 gp12 0可与多种细胞结合而导致HIV 1感染。由此推论PAG是HIV 1gp12 0在人星形细胞上的新受体 ,同时也可能对HIV 1脑病的治疗开辟一条崭新的途径。PAG是否为HIV 1感染人星形细胞的受体 ,仍有待进一步实验证明。

It was first reported in 1994 that HIV 1 gp120 bound to human fetal astrocytes with a single class of 260 kD binding site.Since then many efforts continue to focus on this putative 260 kD protein molecule(designed as PAG)whether it is a new receptor for gp 120 blinding to the astrocyte in relation to the HIV 1 virus entry.In this study,we present the investigative result by developed speciic murine monoclonal antibodies(McAbs)anti PAG on human fetal astrocytes.These McAbs were characterized for their ability in a series of functional analysis of the PAG such as ELISA,western blot and immunoprecipitation,which were in support of the preliminary result.The PAG may be a new receptor of HIV 1 gp120 which is responsible for both gp120 binding and gp120 mediated elevation of Ca 2+ intracellularly in human astrocytes,and it could represent a new target for treatment of HIV 1 encephalapathy.It remains if the PAG may also be a receptor for HIV 1 virus infection of human astrocytes.