Title | Stromal derived factor-1-induced chemokinesis of cord blood CD34(+) cells (long-term culture-initiating cells) through endothelial cells is mediated by E-selectin. |
Publication Type | Journal Article |
Year of Publication | 1999 |
Authors | Naiyer AJ, Jo DY, Ahn J, Mohle R, Peichev M, Lam G, Silverstein RL, Moore MA, Rafii S |
Journal | Blood |
Volume | 94 |
Issue | 12 |
Pagination | 4011-9 |
Date Published | 1999 Dec 15 |
ISSN | 0006-4971 |
Keywords | Cell Communication, Cell Movement, Cells, Cultured, Chemokine CXCL12, Chemokines, Chemokines, CXC, E-Selectin, Endothelium, Vascular, Fetal Blood, Hematopoietic Stem Cells, Humans |
Abstract | 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. |
Alternate Journal | Blood |
PubMed ID | 10590044 |
Grant List | R01 HL58707 / HL / NHLBI NIH HHS / United States R01 HL61401 / HL / NHLBI NIH HHS / United States R01 HL61849 / HL / NHLBI NIH HHS / United States |