Sulfated Polysaccharides as Potent Inhibitors of HIV‐Induced Syncytium Formation: A New Strategy Towards AIDS Chemotherapy
Sulfated Polysaccharides as Potent Inhibitors of HIV‐Induced Syncytium Formation: A New Strategy Towards AIDS Chemotherapy
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硫酸多糖作为 HIV 诱导的合胞体形成的有效抑制剂：艾滋病化疗的新策略
DOI：
10.1097/00126334-199003050-00005
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
E. Clercq
中科院分区：
文献类型：
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作者：
M. Baba;Dominique Schools;R. Pauwels;H. Nakashima;E. Clercq
由表达于人类免疫缺陷病毒1型（HIV-1）感染的细胞表面的gp 120糖蛋白与未感染的CD 4阳性（CD 4+）细胞的CD 4受体之间的相互作用诱导的多核巨细胞（合胞体）形成可能在获得性免疫缺陷综合征（AIDS）患者的T 4淋巴细胞耗竭中起重要作用。使用双荧光细胞染色技术和荧光激活细胞分选仪（FACS）的细胞分析，我们已经证明，巨细胞形成之间的持续HIV-1感染的HUT-78细胞和未感染的MOLT-4细胞的结果在未感染的CD 4 + MOLT-4细胞的选择性破坏。显然，旁观者CD 4+细胞可以作为HIV-1感染细胞杀伤作用的靶细胞，并且这种杀伤作用之前是靶细胞（未感染）和攻击细胞（感染）之间的融合。戊聚糖多硫酸酯、硫酸葡聚糖和各种其他硫酸化多糖，但不包括肝素，已被证明抑制这种细胞融合过程，从而保护靶CD 4+细胞免受杀伤HIV-1感染细胞的破坏。叠氮胸苷不干扰该过程。假设HIV感染的和未感染的CD 4+细胞之间的融合是AIDS发病机制中的关键事件，特异性干扰该过程的任何化合物在治疗该疾病中可能是治疗上有利的。
Multinucleated giant cell (syncytium) formation induced by the interaction between the gpl20 glycoprotein expressed on the surface of cells infected with human immunodeficiency virus type 1 (HIV-1) and the CD4 receptor of uninfected CD4-positive (CD4+ ) cells may play an important role in the depletion of T4 lymphocytes in acquired immune deficiency syndrome (AIDS) patients. Using a double fluorescence cell-staining technique and analysis of the cells by the fluorescence-activated cell sorter (FACS), we have demonstrated that giant cell formation between persistently HIV-1-infected HUT-78 cells and uninfected MOLT-4 cells results in a selective destruction of the uninfected CD4+ MOLT-4 cells. Apparently, bystander CD4+ cells may serve as targets for the killing effect of the HIV-1-infected cells, and this killing effect is preceded by fusion between the target (uninfected) and aggressor (infected) cells. Pentosan polysulfate, dextran sulfate, and various other sulfated polysaccharides, but not heparin, have proved to inhibit this cell fusion process and hence protect the target CD4+ cells against destruction by the killer HIV-1-infected cells. Azidothymidine does not interfere with this process. Assuming that fusion between HIV-infected and uninfected CD4+ cells is a crucial event in the pathogenesis of AIDS, any compounds that specifically interfere with this process may be therapeutically advantageous in the treatment of this disease.