Hatse Sigrid, Balzarini Jan, Liekens Sandra
Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
Biochem Biophys Res Commun. 2006 Sep 15;348(1):192-9. doi: 10.1016/j.bbrc.2006.07.030. Epub 2006 Jul 17.
Stromal cell-derived factor 1 (CXCL12) is an angiogenic chemokine that is believed to act solely via its cognate receptor CXCR4. Evidence is now provided for the existence of a different CXCL12 binding and signaling receptor on endothelial cells. Bovine aortic endothelial cells (BAECs) strongly expressed CXCR4 and exhibited high binding capacity for fluorescently labeled CXCL12. However, CXCL12 binding was not correlated with the CXCR4 expression level and was virtually unaffected by the specific CXCR4 antagonists AMD3100 or T22. Similar observations were made in endothelial cells of mouse and human origin. Also, AMD3100 failed to block CXCL12 internalization and CXCL12-induced intracellular signal transduction via extracellular signal-regulated kinases 1/2 in BAECs. In contrast, CXCL12 binding and signaling were almost completely inhibited by the CXCR4 antagonist in T-lymphoid SupT1 cells. Together, our data point to the existence of an additional receptor through which CXCL12 exerts its biological effects in endothelial cells.
基质细胞衍生因子1（CXCL12）是一种血管生成趋化因子，据信它仅通过其同源受体CXCR4发挥作用。现在有证据表明内皮细胞上存在一种不同的CXCL12结合和信号传导受体。牛主动脉内皮细胞（BAECs）强烈表达CXCR4，并对荧光标记的CXCL12表现出高结合能力。然而，CXCL12结合与CXCR4表达水平无关，并且几乎不受特异性CXCR4拮抗剂AMD3100或T22的影响。在小鼠和人类来源的内皮细胞中也有类似的观察结果。此外，AMD3100未能阻断BAECs中CXCL12的内化以及CXCL12通过细胞外信号调节激酶1/2诱导的细胞内信号转导。相比之下，CXCR4拮抗剂几乎完全抑制了T淋巴细胞SupT1细胞中CXCL12的结合和信号传导。总之，我们的数据表明存在一种额外的受体，CXCL12通过该受体在内皮细胞中发挥其生物学作用。
