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 sequent ial interaction with adhesion molecules expressed on BM endothelium (BMEC) and chemokine stromal derived factor-1 (SDF-1). However, the mechanism wher eby adhesion molecules regulate the SDF-1-induced transendothelial migratio n process is not known. E-selectin is an endothelial-specific selectin that is constitutively expressed by the BMEC in vivo. Hence, we hypothesized th at E-selectin may mediate SDF-1-induced transendothelial migration of CD34( +) cells. We show that CD34(+) cells express both E-selectin ligand and fuc osyltransferase-VII (FucT-VII). Soluble E-selectin-IgG chimera binds avidly to 75% +/- 10% of CD34(+) cells composed mostly of progenitors and cells w ith long-term culture-initiating cell (LTC-IC) potential. To assess the fun ctional capacity of E-selectin to mediate CD34(+) cell migration in a trans endothelial migration system, CD34(+) cells were placed on transwell plates coated with interleukin-1 beta-activated BMEC. In the absence of SDF-1, th ere 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 LT C-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 endoth elial cells, VEGF-stimulated endothelial cells support transendothelial mig ration 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 po tential is determined in part by sequential interactions with E-selectin an d SDF-1. (C) 1999 by The American Society of Hematology.