How does SDF-1 mediate its effects on primitive hematopoietic cells?
SDF-1 (also called CXCL12) is a member of the large chemokine family but differs from most other family members in its reactivity with a single high-affinity receptor, CXCR4. Strategies that upregulate CXCR4 expression on primitive hematopoietic cells enhance the ability of these cells to engraft transplanted recipients. Conversely, strategies that reduce SDF-1–mediated activation of CXCR4 on primitive hematopoietic cells inhibit this function (6). One mechanism of SDF-1 action may be a simple gradient effect governing the probability of CXCR4-positive cell adhesion to endothelial and/or stromal cells inside the bone marrow. However, there is also increasing evidence that downstream signaling events triggered by SDF-1 binding are critical to the ability of primitive hematopoietic cells to migrate toward an SDF-1 gradient and adhere to stroma (6). CXCR4 is a member of the superfamily of pertussis toxin–sensitive G-protein–coupled serpentine receptors that activate PI3K and hence the pro
