Department of Stem Cell Biology and Regenerative Medicine, Graduate School of Medical Science, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka, 570-8506, Japan.
First Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
Int J Hematol. 2009 Dec;90(5):553-560. doi: 10.1007/s12185-009-0451-x. Epub 2009 Nov 26.
Stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4 are the key regulatory molecules of hematopoietic stem cell (HSC) migration and engraftment to the bone marrow (BM) microenvironment. However, the significance of the ligand-receptor complex on HSC in steady-state BM is not clear. There is currently a lack of information as to how CXCR4 is expressed on HSCs. We herein demonstrate that c-kit(+)Sca-1(+)Lineage(-) (KSL) cells freshly isolated from BM expressed very low to undetectable levels of CXCR4. Two hours of incubation at 37 degrees C quickly up-modulated the receptor expression on KSL cells. Protein synthesis was not required for this early stage up-regulation, thus suggesting the emergence of intracellularly pooled receptors to the cell surface. However, protein synthesis was involved at the later stage of up-regulation. The up-regulated CXCR4 was functional, as evidenced by the fact that the incubated KSL cells more efficiently migrated to the SDF-1 gradient in vitro. Therefore, although KSL cells are able to express functional CXCR4, the receptors are only marginally expressed in the steady-state BM microenvironment. These observations therefore indicate the limited role of the SDF-1-CXCR4 axis on HSC functionality in a static BM environment.
基质细胞衍生因子 1（SDF-1）及其受体 CXCR4 是调节造血干细胞（HSC）迁移并归巢到骨髓（BM）微环境的关键调节分子。然而，配体-受体复合物在 BM 中的 HSC 上的意义尚不清楚。目前尚不清楚 CXCR4 在 HSCs 上是如何表达的。我们在此证明，刚从 BM 中分离的 c-kit(+)Sca-1(+)Lineage(-)（KSL）细胞表达的 CXCR4 水平非常低或无法检测到。在 37°C 孵育 2 小时可快速上调 KSL 细胞上的受体表达。此早期上调不需要蛋白质合成，因此表明细胞内聚集的受体出现在细胞表面。然而，蛋白质合成参与了后期的上调过程。上调的 CXCR4 是有功能的，因为孵育的 KSL 细胞在体外更有效地迁移到 SDF-1 梯度中。因此，尽管 KSL 细胞能够表达功能性的 CXCR4，但在稳态 BM 微环境中，受体的表达仅略有增加。这些观察结果表明，在静态 BM 环境中，SDF-1-CXCR4 轴对 HSC 功能的作用有限。
