The chemokine receptor CXCR4 is expressed within the mast cell lineage andits ligand stromal cell-derived factor-1 alpha acts as a mast cell chemotaxin

In this study we provide evidence that the chemokine stromal cell-derived f actor-1 alpha (SDF-1 alpha) acts as a mast cell chemoattractant through int eractions with its receptor CXCR4 expressed on mast cell progenitors in the blood as well as on in vitro-developed and leukemic mast cells. We found e xpression of CXCR4 on cord blood-derived mast cells (CBMC) and on the human mast cell line HMC-1, analyzed by RNAse protection assay and flow cytometr y. SDF-1 alpha: induced intracellular calcium mobilization in HMC-1 cells a nd was chemotactic for both HMC-1 cells and CBMC. The activity of SDF-1 alp ha was completely blocked by treating the cells with pertussis toxin, indic ating the involvement of G(i)-proteins in the signaling. By applying a tran swell assay we could show that SDF-1 alpha induces migration of a cell popu lation in peripheral blood that is enriched for cells with the capacity to differentiate into mast cells. These findings thus suggest a mechanism by w hich human mast cell progenitors may be recruited from circulation into the tissue.