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Blood, 1 January 2005, Vol. 105, No. 1, pp. 40-48. Prepublished online as a Blood First Edition Paper on August 24, 2004; DOI 10.1182/blood-2004-04-1430. This Article Full Text (PDF) All Versions of this Article: 2004-04-1430v1 105/1/40    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wysoczynski, M. Articles by Ratajczak, M. Z Search for Related Content PubMed PubMed Citation Articles by Wysoczynski, M. Articles by Ratajczak, M. Z Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 15, 2004 Accepted August 20, 2004 Incorporation of CXCR4 into membrane lipid rafts primes homing-related responses of hematopoietic stem/progenitor cells to an SDF-1 gradient Marcin Wysoczynski, Ryan Reca, Janina Ratajczak, Magda Kucia, Neeta Shirvaikar, Marek Honczarenko, Michael Mills, Jens Wanzeck, Anna Janowska-Wieczorek, and Mariusz Z Ratajczak* Stem Cell Biology Program at the James Graham Brown Cancer Center and the Department of Medicine, University of Louisville, Louisville, KY, USA Department of Medicine, University of Alberta and Canadian Blood Services, Edmonton, AB, Canada * Corresponding author; email: mzrata01{at}louisville.edu. We found that supernatants of leukapheresis products (SLP) of patients mobilized with G-CSF or the various components of SLP (fibrinogen, fibronectin, soluble VCAM-1, ICAM-1 and uPAR) increase the chemotactic responses of hematopoietic stem/progenitor cells (HSPC) to stromal-derived factor (SDF)-1. However, alone they do not chemoattract HSPC but increase/prime the cells chemotactic responses to a low/threshold dose of SDF-1. We observed that SLP increased calcium flux, phosphorylation of MAPK p42/44 and AKT, secretion of matrix metalloproteinases and adhesion to endothelium in CD34+ cells. Furthermore, SLP increased SDF-dependent actin polymerization and significantly enhanced the homing of human cord blood (CB) and bone marrow (BM)-derived CD34+ cells in a NOD/SCID mice transplant model. Moreover, sensitization/priming of cell chemotaxis to an SDF-1 gradient was dependent on cholesterol content in the cell membrane and on incorporation of the SDF-1 binding receptor CXCR4 and the small GTP-ase Rac-1 into membrane lipid rafts. This colocalization of CXCR4 and Rac-1 in lipid rafts facilitated GTP binding/activation of Rac-1. Hence we postulate that CXCR4 could be primed by various factors related to leukapheresis/mobilization that increase its association with membrane lipid rafts, allowing the HSPC to better sense the SDF-1 gradient. This may partly explain why HSPC from mobilized peripheral blood leukapheresis products engraft faster in patients than those from BM or CB. Based on our findings we suggest (i) the homing of HSPC is optimal when CXCR4 is incorporated in membrane lipid rafts and (ii) ex vivo priming of HSPC with some of the SLP-related molecules before transplantation could increase their engraftment. 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