Hidalgo A, Sanz-Rodríguez F, Rodríguez-Fernández J L, Albella B, Blaya C, Wright N, Cabañas C, Prósper F, Gutierrez-Ramos J C, Teixidó J
Centro de Investigaciones Biológicas, Department of Immunology, Madrid, Spain.
Exp Hematol. 2001 Mar;29(3):345-55. doi: 10.1016/s0301-472x(00)00668-8.
Stromal cell-derived factor-1alpha (SDF-1alpha) is a potent chemoattractant for hematopoietic progenitor cells (HPC), suggesting that it could play an important role during their migration within or to the bone marrow (BM). The integrin VLA-4 mediates HPC adhesion to BM stroma by interacting with CS-1/fibronectin and VCAM-1. It is required during hematopoiesis and homing of HPC to the BM. As HPC migration in response to SDF-1alpha might require dynamic regulation of integrin function, we investigated if SDF-1alpha could modulate VLA-4 function on BM CD34(hi) cells.CD34(hi) BM cells and hematopoietic cell lines were tested for the effect of SDF-1alpha on VLA-4-dependent adhesion to CS-1/fibronectin and VCAM-1, as well as to BM stroma. CD34(hi) BM cells that adhered to VLA-4 ligands after SDF-1alpha treatment were characterized in colony-forming and long-term culture-initiating cell (LTC-IC) assays.SDF-1alpha rapidly (1 minute) and transiently upregulated the adhesion of CD34(hi) BM cells and hematopoietic cell lines to both CS-1/fibronectin and VCAM-1, and to BM stromal cells. The upregulation of VLA-4-dependent cell adhesion by SDF-1alpha targeted primitive LTC-IC as well as committed CD34(hi) cells. SDF-1alpha-triggered enhancement in VLA-4 function was inhibited by pertussis toxin (PTx) and cytochalasin D, indicating the involvement of G(i) protein downstream signaling and an intact cytoskeleton. Instead, activation of p44/42 MAP kinases by SDF-1alpha did not functionally correlate with enhancement of VLA-4-dependent cell adhesion. Modulation of VLA-4-mediated CD34(hi) BM cell adhesion by SDF-1alpha could play a key role in their migration within and to the BM and therefore influence their proliferation and differentiation.
基质细胞衍生因子-1α（SDF-1α）是造血祖细胞（HPC）的一种强效趋化因子，这表明它在HPC迁移至骨髓（BM）内或骨髓的过程中可能发挥重要作用。整合素VLA-4通过与CS-1/纤连蛋白和血管细胞黏附分子-1（VCAM-1）相互作用介导HPC与BM基质的黏附。在造血过程以及HPC归巢至BM的过程中，VLA-4是必需的。由于HPC对SDF-1α的迁移可能需要整合素功能的动态调节，我们研究了SDF-1α是否能调节BM CD34(hi)细胞上的VLA-4功能。检测了SDF-1α对CD34(hi) BM细胞和造血细胞系与CS-1/纤连蛋白、VCAM-1以及BM基质的VLA-4依赖性黏附的影响。对经SDF-1α处理后黏附于VLA-4配体的CD34(hi) BM细胞进行集落形成和长期培养起始细胞（LTC-IC）分析。SDF-1α迅速（1分钟）且短暂地上调了CD34(hi) BM细胞和造血细胞系与CS-1/纤连蛋白、VCAM-1以及BM基质细胞的黏附。SDF-1α对VLA-4依赖性细胞黏附的上调作用针对原始LTC-IC以及定向的CD34(hi)细胞。百日咳毒素（PTx）和细胞松弛素D抑制了SDF-1α触发的VLA-4功能增强，表明G(i)蛋白下游信号传导以及完整的细胞骨架参与其中。相反，SDF-1α对p44/42丝裂原活化蛋白激酶的激活与VLA-4依赖性细胞黏附的增强在功能上并无关联。SDF-1α对VLA-4介导的CD34(hi) BM细胞黏附的调节可能在其在BM内迁移至BM的过程中起关键作用，因此影响它们的增殖和分化。
