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Blood, 1 May 2006, Vol. 107, No. 9, pp. 3503-3510. Prepublished online as a Blood First Edition Paper on January 26, 2006; DOI 10.1182/blood-2005-10-3932. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-10-3932v1 107/9/3503    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Qian, H. Articles by Ekblom, M. Search for Related Content PubMed PubMed Citation Articles by Qian, H. Articles by Ekblom, M. Related Collections Hematopoiesis and Stem Cells Cell Adhesion and Motility Stem Cells in Hematology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Contribution of 6 integrins to hematopoietic stem and progenitor cell homing to bone marrow and collaboration with 4 integrins Hong Qian, Karl Tryggvason, Sten Eirik Jacobsen, and Marja Ekblom From the Hematopoietic Stem Cell Laboratory; Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, and the Department of Hematology, Lund University Hospital, Lund, Sweden; and Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden. The laminin receptor integrin 6 chain is ubiquitously expressed in human and mouse hematopoietic stem and progenitor cells. We have studied its role for homing of stem and progenitor cells to mouse hematopoietic tissues in vivo. A function-blocking anti–integrin 6 antibody significantly reduced progenitor cell homing to bone marrow (BM) of lethally irradiated mice, with a corresponding retention of progenitors in blood. Remarkably, the anti–integrin 6 antibody profoundly inhibited BM homing of long-term multilineage engrafting stem cells, studied by competitive repopulation assay and analysis of donor-derived lymphocytes and myeloid cells in blood 16 weeks after transplantation. A similar profound inhibition of long-term stem cell homing was obtained by using a function-blocking antibody against 4 integrin, studied in parallel. Furthermore, the anti–integrin 6 and 4 antibodies synergistically inhibited homing of short-term repopulating stem cells. Intravenous injection of anti–integrin 6 antibodies, in contrast to antibodies against 4 integrin, did not mobilize progenitors or enhance cytokine-induced mobilization by G-CSF. Our results provide the first evidence for a distinct functional role of integrin 6 receptor during hematopoietic stem and progenitor cell homing and collaboration of 6 integrin with 4 integrin receptors during homing of short-term stem cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Grassinger, D. N. Haylock, M. J. Storan, G. O. Haines, B. Williams, G. A. Whitty, A. R. Vinson, C. L. Be, S. Li, E. S. Sorensen, et al. Thrombin-cleaved osteopontin regulates hemopoietic stem and progenitor cell functions through interactions with {alpha}9{beta}1 and {alpha}4{beta}1 integrins Blood, July 2, 2009; 114(1): 49 - 59. [Abstract] [Full Text] [PDF] R. H. Lee, M. J. Seo, A. A. Pulin, C. A. Gregory, J. Ylostalo, and D. J. Prockop The CD34-like protein PODXL and {alpha}6-integrin (CD49f) identify early progenitor MSCs with increased clonogenicity and migration to infarcted heart in mice Blood, January 22, 2009; 113(4): 816 - 826. [Abstract] [Full Text] [PDF] L. Xin, R. U. Lukacs, D. A. Lawson, D. Cheng, and O. N. Witte Self-Renewal and Multilineage Differentiation In Vitro from Murine Prostate Stem Cells Stem Cells, November 1, 2007; 25(11): 2760 - 2769. [Abstract] [Full Text] [PDF] H. Qian, E. Georges-Labouesse, A. Nystrom, A. Domogatskaya, K. Tryggvason, S. E. W. Jacobsen, and M. Ekblom Distinct roles of integrins {alpha}6 and {alpha}4 in homing of fetal liver hematopoietic stem and progenitor cells Blood, October 1, 2007; 110(7): 2399 - 2407. [Abstract] [Full Text] [PDF] C. Selleri, P. Ragno, P. Ricci, V. Visconte, N. Scarpato, M. V. Carriero, B. Rotoli, G. Rossi, and N. Montuori The metastasis-associated 67-kDa laminin receptor is involved in G-CSF-induced hematopoietic stem cell mobilization Blood, October 1, 2006; 108(7): 2476 - 2484. [Abstract] [Full Text] [PDF] H. Bonig, K.-H. Chang, B. Nakamoto, and T. Papayannopoulou The p67 laminin receptor identifies human erythroid progenitor and precursor cells and is functionally important for their bone marrow lodgment Blood, August 15, 2006; 108(4): 1230 - 1233. [Abstract] [Full Text] [PDF]

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