The chemokine SDF-1 stimulates integrin-mediated arrest of CD34+ cells on vascular endothelium under shear flow

摘要: The chemokine SDF-1 plays a central role in the repopulation of bone marrow (BM) by circulating CD34(+) progenitors, but mechanisms its action remain obscure. To extravasate to target tissue, blood-borne cell must arrest firmly on vascular endothelium. Murine hematopoietic progenitors were recently shown vivo roll along BM microvessels that display selectins and integrins. We now show is constitutively expressed human In vitro, cells establish efficient rolling P-selectin, E-selectin, CD44 ligand hyaluronic acid under physiological shear flow. ICAM-1 alone did not tether flow, but, presence surface-bound SDF-1, endothelial selectin rapidly developed firm adhesion surface, mediated an interaction between integrin ligand, which coimmobilized with SDF-1. Human accumulated efficiently TNF-activated umbilical cord absence they required immobilized develop integrin-mediated spreading. selectins, also promoted VLA-4-mediated, Gi protein-dependent tethering VCAM-1 our knowledge, this first demonstration endothelium crucial for translating into increasing adhesiveness integrins VLA-4 LFA-1 their respective ligands, ICAM-1.