The chemokine receptor CXCR4 is expressed within the mast cell lineage and its ligand stromal cell-derived factor-1alpha acts as a mast cell chemotaxin.
In this study we provide evidence that the chemokine stromal cell-derived factor-1alpha (SDF-1alpha) acts as a mast cell chemoattractant through interactions 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 expression 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 cytometry. SDF-1alpha induced intracellular calcium mobilization in HMC-1 cells and was chemotactic for both HMC-1 cells and CBMC. The activity of SDF-1alpha was completely blocked by treating the cells with pertussis toxin, indicating the involvement of Gi-proteins in the signaling. By applying a transwell assay we could show that SDF-1alpha induces migration of a cell population in peripheral blood that is enriched for cells with the capacity to differentiate into mast cells. These findings thus suggest a mechanism by which human mast cell progenitors may be recruited from circulation into the tissue.
Juremalm
M
M
Research Group on Mast Cell Biology, Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
Hjertson
M
M
Olsson
N
N
Harvima
I
I
Nilsson
K
K
Nilsson
G
G
D002118:Calcium / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology*; D002630:Chemotactic Factors / Q000494:pharmacology*; D006801:Humans; D008407:Mast Cells / Q000737:chemistry* / Q000502:physiology; D015513:Oncogene Proteins / Q000032:analysis; D019009:Proto-Oncogene Proteins c-kit; D019718:Receptors, CXCR4 / Q000032:analysis*; D019089:Stem Cell Factor / Q000494:pharmacology; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D015513:Oncogene Proteins; D019718:Receptors, CXCR4; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit; D002118:Calcium