Majka M, Rozmyslowicz T, Honczarenko M, Ratajczak J, Wasik M A, Gaulton G N, Ratajczak M Z
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Leukemia. 2000 Oct;14(10):1821-32. doi: 10.1038/sj.leu.2401891.
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-1alpha, MIP-1beta 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.
本研究的目的是更深入了解与HIV相关的趋化因子-趋化因子受体轴在人类造血过程中的作用。为解决这一问题，我们对35种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，以及通过SDF-1、MIP-1α、MIP-1β和RANTES影响表达CXCR4和/或CCR5的细胞生长的能力，评估了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造血细胞被X4和R5 HIV毒株感染的能力。这些结果表明：（1）与HIV相关的受体在人类造血细胞系上广泛表达；（2）SDF-1对CXCR4的刺激在几种造血细胞系中比受体特异性β趋化因子对CCR5的刺激更有效地诱导钙流和趋化性；（3）趋化因子不调节造血细胞的增殖；最后（4）造血细胞被HIV-1感染的能力可能受到内源性分泌趋化因子的自动调节。这些数据进一步阐明了与HIV相关的趋化因子-趋化因子受体轴在人类造血过程中的作用以及造血细胞与HIV的相互作用。
