Biological significance of the expression of HIV-related chemokine coreceptors (CCR5 and CXCR4) and their ligands by human hematopoietic cell lines
Biological significance of the expression of HIV-related chemokine coreceptors (CCR5 and CXCR4) and their ligands by human hematopoietic cell lines
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DOI：
10.1038/sj.leu.2401891
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发表时间：
2000-10-01
期刊：
影响因子：
11.4
通讯作者：
Ratajczak, MZ
中科院分区：
文献类型：
--
作者：
Majka, M;Rozmyslowicz, T;Ratajczak, MZ
本研究的目的是更多地了解 HIV 相关趋化因子-趋化因子受体轴在人类造血中的作用。为了解决这个问题，我们对 35 个选定的造血细胞系进行了 CD4、CXCR4 和 CCR5 表达的表型分析。接下来，我们通过钙流和趋化性测定以及 SDF-1 MIP-1 α、MIP-1 β 和 RANTES 影响表达 CXCR4 和/或 CCR5 的细胞生长的能力来评估这些趋化因子受体的功能。最后，我们研究了人类造血细胞系是否可能分泌一些与HIV相关的趋化因子，以及内源性分泌的趋化因子是否可能干扰X4和R5 HIV毒株对造血细胞的感染性。这些结果表明：（1）HIV相关受体在人类造血细胞系上广泛表达； (2) SDF-1刺激CXCR4比受体特异性β趋化因子刺激CCR5更有效地诱导几种造血细胞系中的钙流动和趋化性； (3)趋化因子不调节造血细胞的增殖；最后(4) HIV-1对造血细胞的感染性可能是由内源性分泌的趋化因子自动调节的。这些数据进一步阐明了 HIV 相关趋化因子-趋化因子受体轴在人类造血中的作用以及造血细胞与 HIV 的相互作用。
The aim of this study was to learn more about the role of the HIV-related chemokine-chemokine receptor axes in human hematopoiesis. To address this issue we phenotyped 35 selected hematopoietic cell lines for the expression of CD4, CXCR4 and CCR5. We next evaluated the functionality of these chemokine receptors by calcium flux and chemotaxis assays, and by the ability of SDF-1 MIP-1 alpha, MIP-1 beta and RANTES to influence the growth of the cells expressing CXCR4 and/or CCR5. Lastly, we examined whether human hematopoietic cell lines may secrete some HIV-related chemokines, and whether endogenously secreted chemokines might interfere with the infectability of hematopoietic cells by X4 and R5 HIV strains. These results demonstrate that: (1) HIV-related receptors are widely expressed on human hematopoietic cell lines; (2) stimulation of CXCR4 by SDF-1 induces calcium flux and chemotaxis in several hematopoietic cell lines more efficiently than stimulation of CCR5 by receptor-specific beta-chemokines; (3) chemokines do not regulate proliferation of the hematopoietic cells; and finally (4) infectability of the hematopoietic cells by HIV-1 may be auto-modulated by endogenously secreted chemokines. These data shed more light on the role of HIV-related chemokine-chemokine receptors axes in human hematopoiesis and interaction of hematopoietic cells with HIV.