| Autor: |
Naiyer, Afzal J., Jo, Deog-Yeon, Ahn, Jongcheol, Mohle, Robert, Peichev, Mario, Lam, George, Silverstein, Roy L., Moore, Malcolm A.S., Rafii, Shahin |
| Zdroj: |
Blood; December 1999, Vol. 94 Issue: 12 p4011-4019, 9p |
| Abstrakt: |
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-1β–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. |
| Databáze: |
Supplemental Index |
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