Hartman Institute for Therapeutic Organ Regeneration

Stromal derived factor-1-induced chemokinesis of cord blood CD34(+) cells (long-term culture-initiating cells) through endothelial cells is mediated by E-selectin.

TitleStromal derived factor-1-induced chemokinesis of cord blood CD34(+) cells (long-term culture-initiating cells) through endothelial cells is mediated by E-selectin.
Publication TypeJournal Article
Year of Publication1999
AuthorsNaiyer AJ, Jo DY, Ahn J, Mohle R, Peichev M, Lam G, Silverstein RL, Moore MA, Rafii S
JournalBlood
Volume94
Issue12
Pagination4011-9
Date Published1999 Dec 15
ISSN0006-4971
KeywordsCell 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 JournalBlood
PubMed ID10590044
Grant ListR01 HL58707 / HL / NHLBI NIH HHS / United States
R01 HL61401 / HL / NHLBI NIH HHS / United States
R01 HL61849 / HL / NHLBI NIH HHS / United States

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