Ratajczak Mariusz Z, Kim Chihwa, Janowska-Wieczorek Anna, Ratajczak Janina
Stem Cell Biology Program at the James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
ScientificWorldJournal. 2012;2012:758512. doi: 10.1100/2012/758512. Epub 2012 Jun 4.
The α-chemokine stromal derived factor 1 (SDF-1), which binds to the CXCR4 and CXCR7 receptors, directs migration and homing of CXCR4+ hematopoietic stem/progenitor cells (HSPCs) to bone marrow (BM) and plays a crucial role in retention of these cells in stem cell niches. However, this unique role of SDF-1 has been recently challenged by several observations supporting SDF-1-CXCR4-independent BM homing. Specifically, it has been demonstrated that HSPCs respond robustly to some bioactive lipids, such as sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P), and migrate in response to gradients of certain extracellular nucleotides, including uridine triphosphate (UTP) and adenosine triphosphate (ATP). Moreover, the responsiveness of HSPCs to an SDF-1 gradient is enhanced by some elements of innate immunity (e.g., C3 complement cascade cleavage fragments and antimicrobial cationic peptides, such as cathelicidin/LL-37 or β2-defensin) as well as prostaglandin E2 (PGE2). Since all these factors are upregulated in BM after myeloblative conditioning for transplantation, a more complex picture of homing emerges that involves several factors supporting, and in some situations even replacing, the SDF-1-CXCR4 axis.
α趋化因子基质衍生因子1（SDF-1）与CXCR4和CXCR7受体结合，引导CXCR4+造血干/祖细胞（HSPCs）迁移并归巢至骨髓（BM），并在将这些细胞保留在干细胞龛中发挥关键作用。然而，SDF-1的这一独特作用最近受到了一些支持不依赖SDF-1-CXCR4的BM归巢的观察结果的挑战。具体而言，已经证明HSPCs对一些生物活性脂质，如1-磷酸鞘氨醇（S1P）和1-磷酸神经酰胺（C1P）有强烈反应，并对某些细胞外核苷酸的梯度作出反应而迁移，包括三磷酸尿苷（UTP）和三磷酸腺苷（ATP）。此外，先天免疫的一些成分（如C3补体级联裂解片段和抗菌阳离子肽，如cathelicidin/LL-37或β2-防御素）以及前列腺素E2（PGE2）可增强HSPCs对SDF-1梯度的反应性。由于在骨髓清髓预处理以进行移植后，所有这些因子在BM中均上调，因此出现了一幅更复杂的归巢图景，其中涉及几个支持甚至在某些情况下替代SDF-1-CXCR4轴的因子。
