Increased CCR5 and CXCR4 expression in Ethiopians living in Israel: Environmental and constitutive factors
Increased CCR5 and CXCR4 expression in Ethiopians living in Israel: Environmental and constitutive factors
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DOI：
10.1006/clim.2001.5040
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发表时间：
2001-07-01
影响因子：
8.6
通讯作者：
Bentwich, Z
中科院分区：
文献类型：
--
作者：
Kalinkovich, A;Borkow, G;Bentwich, Z
HIV 辅助受体在决定易感性和 HIV 细胞趋向性方面发挥着重要作用。目前的工作研究了在以色列埃塞俄比亚移民（ETH）的淋巴细胞和单核细胞上发现的这些辅助受体的高表达是否是环境和/或组成性遗传因素的结果。对抵达以色列后不久的 26 个 ETH（新 ETH）、7 年来在以色列的 22 个 ETH 以及 20 个白人以色列人（非 ETH）进行的研究使我们能够解决这个问题。与旧ETH组和非ETH组相比，新ETH组的活化HLA-DR(+)CD4(+)和CD38(+)CD8(+)细胞水平升高(P < 0.01)，这很可能与慢性蠕虫感染有关。在所有组中，活化的 CD4(+) 细胞的表面 CCR5 表达，即 CCR5(+) 细胞的百分比和 CCR5 分子/细胞的数量，均高于未活化的 CD4(+) 细胞（分别为 2 至 3 倍和 8 至 31 倍）。然而，无论是激活的还是非激活的CD4+细胞，CCR5的表达在两个ETH组中均高于非ETH组。所有组中未激活的 CD4(+) 细胞中 CXCR4 的表达均较高，并且 ETH 组中激活和未激活的 CD4(+) 细胞中的 CXCR4 表达也高于非 ETH 组。这些发现表明，除了环境因素引起的免疫激活之外，构成性因素也是 ETH 的 CD4+ 细胞上 CCR5 和 CXCR4 表达升高的原因。 HIV 辅助受体表达的增加可能使 ETH 更容易受到 HIV 感染，并可能部分解释艾滋病在埃塞俄比亚和非洲其他地区的迅速传播。 (C) 2001 年学术出版社。
HIV coreceptors play a major role in determining susceptibility and HIV cell tropism. The present work studied whether the high expression of these coreceptors found on lymphocytes and monocytes of Ethiopian immigrants to Israel (ETH) is the result of environmental and/or constitutive genetic factors. The study of 26 ETH shortly after their arrival to Israel (new ETH), 22 ETH in Israel over 7 years told ETH), and 20 Caucasian Israelis (non-ETH) enabled us to address this issue. The new ETH had elevated levels of activated HLA-DR(+)CD4(+) and CD38(+)CD8(+) cells in comparison with both old ETH and non-ETH groups (P < 0.01), most probably related to chronic helminthic infections. Surface CCR5 expression, i.e., the percentage of CCR5(+) cells and the number of CCR5 molecules/cell, was higher (2- to 3- and 8- to 31-fold, respectively) in activated than in nonactivated CD4(+) cells, in all groups. However, CCR5 expression, in both activated and nonactivated CD4(+) cells, was higher in both ETH groups than in the non-ETH group. CXCR4 expression was higher in nonactivated CD4(+) cells in all groups and was also higher in both ETH groups, in both activated and nonactivated CD4(+) cells, than in the non-ETH group. These findings suggest that constitutive factors, in addition to immune activation caused by environmental factors, account for the elevated expression of CCR5 and CXCR4 on CD4(+) cells of ETH. This increased HIV coreceptor expression may make ETH more susceptible to HIV infection and may account in part for the rapid spread of AIDS in Ethiopia and the rest of Africa as well. (C) 2001 Academic Press.