期刊
EXPERIMENTAL HEMATOLOGY
卷 29, 期 3, 页码 345-355出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/S0301-472X(00)00668-8
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Objective. Stromal cell-derived factor-1 alpha (SDF-1 alpha) is a potent chemoattractant for hematopoietic progenitor cells (HPC), suggesting that it could play an important role during their migration within or to the bone marrow (BM). The integrin VLA-4 mediates HPC adhesion to BM stroma by interacting with CS-1/fibronectin and VCAM-1, It is required during hematopoiesis and homing of HPC to the BM, As HPC migration in response to SDF-1 alpha might require dynamic regulation of integrin function, we investigated if SDF-1 alpha could modulate VLA-4 function on BM CD34(hi) cells. Materials and Methods. CD34(hi) BM cells and hematopoietic cell lines were tested for the effect of SDF-1 alpha on VLA-4-dependent adhesion to CS-1/fibronectin and VCAM-1, as well as to BM stroma, CD34(hi) BM cells that adhered to VLA-4 ligands after SDF-1 alpha treatment were characterized in colony-forming and long-term culture-initiating cell (LTC-IC) assays. Results, SDF-1 alpha rapidly (1 minute) and transiently upregulated the adhesion of CD34(hi) BM cells and hematopoietic cell lines to both CS-1/fibronectin and VCAM-1, and to BM stromal tells. The upregulation of VLA-4-dependent cell adhesion by SDF-1 alpha. targeted primitive LTC-IC as well as committed CD34(hi) cells. SDF-1 alpha -triggered enhancement in VLA-il function was inhibited by pertussis toxin (PTx) and cytochalasin D, indicating the involvement of G(i) protein downstream signaling and an intact cytoskeleton, Instead, activation of p44/42 MAP kinases by SDF-1 alpha did not functionally correlate with enhancement of VLA-4-dependent cell adhesion, Conclusions, Modulation of VLA-4-mediated CD34(hi) BM cell adhesion by SDF-1 alpha could play a key role in their migration within and to the BR;I and therefore influence their proliferation and differentiation. (C) 2001 InternationaI Society for Experimental Hematology. Published by Elsevier Science Inc.
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