Department of Hematology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Int J Hematol. 2010 Mar;91(2):293-302. doi: 10.1007/s12185-009-0488-x.
This study aims to investigate the role of stromal cell-derived factor 1alpha (SDF-1alpha) and its receptor CXCR4 in cellular infiltration of the lung in differentiation syndrome (DS). The acute promyelocytic leukemia (APL) NB4 cells and freshly prepared APL cells from the patients were differentiated by all-trans retinoic acid (ATRA). The expression of SDF-1alpha in human lung tissues was examined by RT-PCR and Western blot analysis. The cells were subjected to adhesion, migration or invasion assays, and co-cultured with human lung tissues in a microgravity rotary cell culture system to examine cellular infiltration in situ. ATRA-differentiated cells expressed high levels of CXCR4, and adhered more strongly to matrigel. Their ability to migrate and invade was enhanced by SDF-1alpha and lung homogenate, and diminished by pre-treatment with an anti-CXCR4 blocking antibody. SDF-1alpha was expressed in the lung tissues of all seven human donors. ATRA-differentiated NB4 cells infiltrated into lung tissues, and this was reduced by pre-treatment with an anti-CXCR4 blocking antibody. The interaction of SDF-1alpha and CXCR4 plays an important role in pulmonary cellular infiltration during DS, suggesting that targeting SDF-1alpha and CXCR4 may provide the basis for potential treatments in the management of DS.
本研究旨在探讨基质细胞衍生因子 1α（SDF-1α）及其受体 CXCR4 在分化综合征（DS）中肺细胞浸润中的作用。急性早幼粒细胞白血病（APL）NB4 细胞和患者新制备的 APL 细胞通过全反式视黄酸（ATRA）分化。通过 RT-PCR 和 Western blot 分析检测人肺组织中 SDF-1α的表达。对细胞进行粘附、迁移或侵袭试验，并在微重力旋转细胞培养系统中与人肺组织共培养，原位检测细胞浸润。ATRA 分化的细胞表达高水平的 CXCR4，与基质胶的粘附力更强。SDF-1α 和肺匀浆增强了它们的迁移和侵袭能力，而用抗 CXCR4 阻断抗体预处理则减弱了这种能力。SDF-1α 在所有 7 位人类供体的肺组织中均有表达。ATRA 分化的 NB4 细胞浸润到肺组织中，而用抗 CXCR4 阻断抗体预处理则减少了这种浸润。SDF-1α 和 CXCR4 的相互作用在 DS 期间的肺细胞浸润中发挥重要作用，提示靶向 SDF-1α 和 CXCR4 可能为 DS 管理中的潜在治疗提供基础。
