Incorporation of CXCR4 into membrane lipid rafts primes homing-related responses of hematopoietic stem/progenitor cells to an SDF-1 gradient.

摘要: We found that supernatants of leukapheresis products (SLPs) patients mobilized with granulocyte-colony-stimulating factor (G-CSF) or the various components SLPs (fibrinogen, fibronectin, soluble vascular cell adhesion molecule-1 [VCAM-1], intercellular [ICAM-1], and urokinase plasminogen activator receptor [uPAR]) increase chemotactic responses hematopoietic stem/progenitor cells (HSPCs) to stromal-derived factor-1 (SDF-1). However, alone they do not chemoattract HSPCs, but prime cells' a low threshold dose SDF-1. observed increased calcium flux, phosphorylation mitogen-activated protein kinase (MAPK) p42/44 AKT, secretion matrix metalloproteinases, endothelium in CD34+ cells. Furthermore, SDF-dependent actin polymerization significantly enhanced homing human cord blood (CB)- bone marrow (BM)-derived NOD/SCID mouse transplantation model. Moreover, sensitization priming chemotaxis an SDF-1 gradient was dependent on cholesterol content membrane incorporation binding CXCR4 small GTPase Rac-1 into lipid rafts. This colocalization rafts facilitated guanosine triphosphate (GTP) binding/activation Rac-1. Hence, we postulate could be primed by factors related mobilization its association rafts, allowing HSPCs better sense gradient. may partially explain why from peripheral engraft more quickly than those BM CB. Based our findings, suggest is optimal when incorporated ex vivo some SLP-related molecules before their engraftment.