Nonpeptide mediators in the hematopoietic microenvironment.

Migration of hematopoietic stem and progenitor cells (HPCs) is controlled by chemotactic factors released in the hematopoietic microenvironment. In particular, the chemokine SDF-1, which activates the G protein-coupled receptor (GPR) CXCR4, plays an important role in progenitor cell mobilization and homing. However, we provide evidence that ligands of other GPRs similarly act on CD34(+) hematopoietic progenitors. These ligands comprise non-peptide mediators, including the cysteinyl-leukotriene receptor CysLT1, and stimulate migration and integrin-dependent adhesion of HPCs. Moreover, continuous activation of a GPR by a specific ligand upregulates the responsiveness of other GPRs to their corresponding ligands. These findings suggest that HPC migration may not depend on a single chemokine receptor (e.g., CXCR4). Rather, mobilization and homing of HPCs involve several GPRs, which interact with each other as well as with adhesion molecules. Pharmacological activation and inhibition of the GPR may allow HPC mobilization and homing to be modulated.