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Blood, 15 March 2004, Vol. 103, No. 6, pp. 2071-2078. Prepublished online as a Blood First Edition Paper on November 6, 2003; DOI 10.1182/blood-2003-06-2099. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-06-2099v1 2003-06-2099v2 103/6/2071    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 Ratajczak, J. Articles by Ratajczak, M. Z. Search for Related Content PubMed PubMed Citation Articles by Ratajczak, J. Articles by Ratajczak, M. Z. Related Collections Hematopoiesis and Stem Cells Immunobiology Transplantation Cell Adhesion and Motility Signal Transduction Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Mobilization studies in mice deficient in either C3 or C3a receptor (C3aR) reveal a novel role for complement in retention of hematopoietic stem/progenitor cells in bone marrow Janina Ratajczak, Ryan Reca, Magda Kucia, Marcin Majka, Daniel J. Allendorf, Jarek T. Baran, Anna Janowska-Wieczorek, Rick A. Wetsel, Gordon D. Ross, and Mariusz Z. Ratajczak From the Stem Cell Biology Program, James Graham Brown Cancer Center, University of Louisville, Louisville, KY; the Department of Medicine, University of Alberta and Canadian Blood Services, Edmonton, AB, Canada; the European Stem Cell Therapeutic Excellence Center, Medical College, Jagiellonian University, Cracow, Poland; and the Institute of Molecular Medicine, University of Texas–Houston, Houston, TX. The mechanisms regulating the homing/mobilization of hematopoietic stem/progenitor cells (HSPCs) are not fully understood. In our previous studies we showed that the complement C3 activation peptide, C3a, sensitizes responses of HSPCs to stromal-derived factor 1 (SDF-1). In this study, mobilization was induced with granulocyte colony-stimulating factor (G-CSF) in both C3-deficient (C3–/–) and C3a receptor–deficient (C3aR–/–) mice as well as in wild-type (wt) mice in the presence or absence of a C3aR antagonist, SB 290157. The data indicated (1) significantly increased G-CSF–induced mobilization in C3–/– and C3aR–/– mice compared with wt mice, (2) significantly accelerated and enhanced G-CSF–induced mobilization in wt, but not in C3–/– or C3aR–/–, mice treated with SB 290157, and (3) deposition of C3b/iC3b fragments onto the viable bone marrow (BM) cells of G-CSF–treated animals. Furthermore, mobilization studies performed in chimeric mice revealed that wt mice reconstituted with C3aR–/– BM cells, but not C3aR–/– mice reconstituted with wt BM cells, are more sensitive to G-CSF–induced mobilization, suggesting that C3aR deficiency on graft-derived cells is responsible for this increased mobilization. Hence we suggest that C3 is activated in mobilized BM into C3a and C3b, and that the C3a-C3aR axis plays an important and novel role in retention of HSPCs (by counteracting mobilization) by increasing their responsiveness to SDF-1, the concentration of which is reduced in BM during mobilization. The C3a-C3aR axis may prevent an uncontrolled release of HSPCs into peripheral blood. These data further suggest that the C3aR antagonist SB 290157 could be developed as a drug to mobilize HSPCs for transplantation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: I. U. Schraufstatter, R. G. DiScipio, M. Zhao, and S. K. Khaldoyanidi C3a and C5a Are Chemotactic Factors for Human Mesenchymal Stem Cells, Which Cause Prolonged ERK1/2 Phosphorylation J. Immunol., March 15, 2009; 182(6): 3827 - 3836. [Abstract] [Full Text] [PDF] W. Wu, H. Lee, M. Wysoczynski, M. Kucia, J. Ratajczak, and M. Z Ratajczak Novel Observation That Mice Lacking the Fifth Complement Cascade Protein Component (C5) Are Very Poor Stem Cell Mobilizers Explained by Defective Egress of Granulocytes: A Novel Role for Bone Marrow Granulocytes to Act as "ice Breaker" Cells in Facilitating Egress of Hematopoietic Stem/Progenitor Cells Blood (ASH Annual Meeting Abstracts), November 16, 2008; 112(11): 67 - 67. [Abstract] X. Wang, H. Hisha, W. Cui, C. Song, T. Mizokami, S. Okazaki, Q. Li, W. Feng, J. Kato, S. Jiang, et al. The characteristics of hematopoietic stem cells from autoimmune-prone mice and the role of neural cell adhesion molecules in abnormal proliferation of these cells in MRL/lpr mice Haematologica, March 1, 2007; 92(3): 300 - 307. [Abstract] [Full Text] [PDF] R. Reca, M. Wysoczynski, K. Magda, A. Janowska-Wieczorek, J. Ratajczak, and M. Z. Ratajczak Mobilization Studies in Immunodeficient Mice Support a Role of Complement in Modulating the Trafficking of Hematopoietic Stem Cells (HSC) - A Pivotal Role of C3 Cleavage Fragments in Retention and C5 Fragments in Mobilization/Egress of HSC. Blood (ASH Annual Meeting Abstracts), November 16, 2006; 108(11): 3375 - 3375. [Abstract] [PDF] D. E. Cramer, D. J. Allendorf, J. T. Baran, R. Hansen, J. Marroquin, B. Li, J. Ratajczak, M. Z. Ratajczak, and J. Yan {beta}-Glucan enhances complement-mediated hematopoietic recovery after bone marrow injury Blood, January 15, 2006; 107(2): 835 - 840. [Abstract] [Full Text] [PDF] R. Reca, M. Wysoczynski, R. Hansen, M. Kucia, A. Janowska-Wieczorek, J. Ratajczak, and M. Z. Ratajczak Immunodeficient Mice Are Poor Mobilizers -Novel Evidence That Demonstrates a Pivotal Role of Complement in Triggering Mobilization of HSPC. Blood (ASH Annual Meeting Abstracts), November 16, 2005; 106(11): 1976 - 1976. [Abstract] H. Boshra, T. Wang, L. Hove-Madsen, J. Hansen, J. Li, A. Matlapudi, C. J. Secombes, L. Tort, and J. O. Sunyer Characterization of a C3a Receptor in Rainbow Trout and Xenopus: The First Identification of C3a Receptors in Nonmammalian Species J. Immunol., August 15, 2005; 175(4): 2427 - 2437. [Abstract] [Full Text] [PDF] A. G. Therien, R. Baelder, and J. Kohl Agonist Activity of the Small Molecule C3aR Ligand SB 290157 J. Immunol., June 15, 2005; 174(12): 7479 - 7480. [Full Text] [PDF] P. M. Chilton, F. Rezzoug, M. Z. Ratajczak, I. Fugier-Vivier, J. Ratajczak, M. Kucia, Y. Huang, M. K. Tanner, and S. T. Ildstad Hematopoietic stem cells from NOD mice exhibit autonomous behavior and a competitive advantage in allogeneic recipients Blood, March 1, 2005; 105(5): 2189 - 2197. [Abstract] [Full Text] [PDF] M. Wysoczynski, R. Reca, J. Ratajczak, M. Kucia, N. Shirvaikar, M. Honczarenko, M. Mills, J. Wanzeck, A. Janowska-Wieczorek, and M. Z. Ratajczak Incorporation of CXCR4 into membrane lipid rafts primes homing-related responses of hematopoietic stem/progenitor cells to an SDF-1 gradient Blood, January 1, 2005; 105(1): 40 - 48. [Abstract] [Full Text] [PDF] M. Kucia, B. Dawn, G. Hunt, Y. Guo, M. Wysoczynski, M. Majka, J. Ratajczak, F. Rezzoug, S. T. Ildstad, R. Bolli, et al. Cells Expressing Early Cardiac Markers Reside in the Bone Marrow and Are Mobilized Into the Peripheral Blood After Myocardial Infarction Circ. Res., December 10, 2004; 95(12): 1191 - 1199. [Abstract] [Full Text] [PDF] A. H. J. Kim, I. D. Dimitriou, M. C. H. Holland, D. Mastellos, Y. M. Mueller, J. D. Altman, J. D. Lambris, and P. D. Katsikis Complement C5a Receptor Is Essential for the Optimal Generation of Antiviral CD8+ T Cell Responses J. Immunol., August 15, 2004; 173(4): 2524 - 2529. [Abstract] [Full Text] [PDF]

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