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Blood, Vol. 93 No. 1 (January 1), 1999:
pp. 149-156
Selective Transendothelial Migration of Hematopoietic Progenitor
Cells: A Role in Homing of Progenitor Cells
Kiyotoshi Imai,
Masanobu Kobayashi,
Jingxin Wang,
Yoichi Ohiro,
Jun-ichi Hamada,
Yuko Cho,
Masahiro Imamura,
Manabu Musashi,
Takeshi Kondo,
Masuo Hosokawa, and
Masahiro Asaka
From the Laboratory of Pathology, Laboratory of Cell Biology, Cancer
Institute, the Department of Pediatrics, the Department of Gerontology
and Oncology, The Third Department of Internal Medicine, Hokkaido
University School of Medicine, Sapporo, Japan.
To elucidate the mechanisms by which hematopoietic progenitor cells
transmigrate via the bone marrow (BM) endothelial cells, we first
established endothelial cell lines from BM and lung, and BM fibroblast
cell lines; then we established an in vitro model of transendothelial
migration of hematopoietic progenitor cells in the presence of
chemoattractants secreted by BM fibroblast cells. The BM endothelial
cells expressed vascular cell adhesion molecule-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 rolling along the endothelial cells. Anti-SDF-1 antibody inhibited the transendothelial migration of
a hematopoietic progenitor cell line, FDCP-2. FDCP-2 that expressed very late activation antigen-4 (VLA-4) and normal progenitor cells transmigrated through BM endothelial cells but not lung endothelial cells, even if in the presence of chemoattractants produced by BM
fibroblasts. Both anti-VLA-4 and anti-VCAM-1 antibodies inhibited the
transendothelial migration of FDCP-2 cells and normal hematopoietic progenitor cells. These findings suggest that the transendothelial migration of hematopoietic progenitor cells is characteristic of BM
endothelial cells, and that VLA-4/VCAM-1 and SDF-1 play important roles
in the transendothelial migration and, consequently, homing of
hematopoietic progenitor cells to BM.
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