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Blood, Vol. 94 No. 12 (December 15), 1999:
pp. 4011-4019
Stromal Derived Factor-1-Induced Chemokinesis of Cord Blood
CD34+ Cells (Long-Term Culture-Initiating Cells) Through
Endothelial Cells Is Mediated by E-Selectin
Afzal J. Naiyer,
Deog-Yeon Jo,
Jongcheol Ahn,
Robert Mohle,
Mario Peichev,
George Lam,
Roy L. Silverstein,
Malcolm A.S. Moore, and
Shahin Rafii
From the Division of Hematology and Oncology, Weill Medical College
of Cornell University, New York, NY; the Laboratory of Developmental
Hematopoiesis, Sloan-Kettering Institute, New York, NY; and the
Tubingen Medical Center, University of Tubingen, Tu- bingen, Germany.
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-1 -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 (VEGF165) 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.

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