Stromal derived factor-1-induced chemokinesis of cord blood CD34(+) cells (long-term culture-initiating cells) through endothelial cells is mediated by E-selectin.
Homing of hematopoietic stem cells to the bone marrow (BM) involves sequential interaction with adhesion molecules expressed on BM endothelium (BMEC) and chemokine stromal derived factor-1 (SDF-1). However, the mechanism whereby adhesion molecules regulate the SDF-1-induced transendothelial migration process is not known. E-selectin is an endothelial-specific selectin that is constitutively expressed by the BMEC in vivo. Hence, we hypothesized that E-selectin may mediate SDF-1-induced transendothelial migration of CD34(+) cells. We show that CD34(+) cells express both E-selectin ligand and fucosyltransferase-VII (FucT-VII). Soluble E-selectin-IgG chimera binds avidly to 75% +/- 10% of CD34(+) cells composed mostly of progenitors and cells with long-term culture-initiating cell (LTC-IC) potential. To assess the functional capacity of E-selectin to mediate CD34(+) cell migration in a transendothelial migration system, CD34(+) cells were placed on transwell plates coated with interleukin-1beta-activated BMEC. In the absence of SDF-1, there was spontaneous migration of 7.0% +/- 1.4% of CD34(+) cells and 14.1% +/- 2.2% of LTC-IC. SDF-1 induced migration of an additional 23.0% +/- 4.4% of CD34(+) cells and 17.6% +/- 3.6% of LTC-IC. Blocking MoAb to E-selectin inhibited SDF-1-induced migration of CD34(+) cells by 42.0% +/- 2.5% and LTC-IC by 90.9% +/- 16.6%. To define the mechanism of constitutive expression of E-selectin by the BMEC in vivo, we have found that vascular endothelial growth factor (VEGF(165)) induces E-selectin expression by cultured endothelial cells. VEGF-stimulated endothelial cells support transendothelial migration of CD34(+) cells that could be blocked by MoAb to E-selectin. These results suggest that trafficking of subsets of CD34(+) cells with LTC-IC potential is determined in part by sequential interactions with E-selectin and SDF-1.
Naiyer
A J
AJ
Division of Hematology, Weill Medical College of Cornell University, New York, NY, USA.
Jo
D Y
DY
Ahn
J
J
Mohle
R
R
Peichev
M
M
Lam
G
G
Silverstein
R L
RL
Moore
M A
MA
Rafii
S
S
D002450:Cell Communication / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D018925:Chemokines / Q000502:physiology; D019743:Chemokines, CXC / Q000502:physiology*; D019040:E-Selectin / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology*; D005312:Fetal Blood; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology*; D006801:Humans
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; D019040:E-Selectin