Faculty Collaboration Database

Stromal derived factor-1-induced chemokinesis of cord blood CD34(+) cells (long-term culture-initiating cells) through endothelial cells is mediated by E-selectin. Blood 1999 Dec 15;94(12):4011-9

Date

12/10/1999

Pubmed ID

10590044

Scopus ID

2-s2.0-0032794412 (requires institutional sign-in at Scopus site)   91 Citations

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.

Author List

Naiyer AJ, Jo DY, Ahn J, Mohle R, Peichev M, Lam G, Silverstein RL, Moore MA, Rafii S

Author

Roy L. Silverstein MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cell Communication
Cell Movement
Cells, Cultured
Chemokine CXCL12
Chemokines
Chemokines, CXC
E-Selectin
Endothelium, Vascular
Fetal Blood
Hematopoietic Stem Cells
Humans