Selective transendothelial migration of hematopoietic progenitor cells: A role in homing of progenitor cells

To elucidate the mechanisms by which hematopoietic progenitor cells transmi grate via the bone marrow (BM) endothelial cells, we first established endo thelial cell lines from BM and lung, and BM fibroblast cell lines; then we established an in vitro model of transendothelial migration of hematopoieti c progenitor cells in the presence of chemoattractants secreted by BM fibro blast cells. The BM endothelial cells expressed vascular cell adhesion mole cule-1 (VCAM-1), but the lung endothelial cells did not. The BM fibroblast cells secreted chemoattractants including stroma cell-derived factor (SDF)- 1,which could attract hematopoietic progenitor cells to BM and activate the adhesion molecules expressed on hematopoietic progenitor cells after rolli ng along the endothelial cells. Anti-SDF-1 antibody inhibited the transendo thelial migration of a hematopoietic progenitor cell line, FDCP-2. FDCP-2 t hat expressed very late activation antigen-4 (VLA-4) and normal progenitor cells transmigrated through BM endothelial cells but not lung endothelial c ells, even if in the presence of chemoattractants produced by BM fibroblast s. Both anti-VLA-4 and anti-VCAM-1 antibodies inhibited the transendothelia l migration of FDCP-2 cells and normal hematopoietic progenitor cells. Thes e findings suggest that the transendothelial migration of hematopoietic pro genitor cells is characteristic of BM endothelial cells, and that VLA-4/VCA M-1 and SDF-1 play important roles in the transendothelial migration and, c onsequently, homing of hematopoietic progenitor cells to BM. (C) 1999 by Th e American Society of Hematology.