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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, 2003November 6, 2003; DOI 10.1182/blood-2003-06-2099. This Article 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 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 Social Bookmarking                   What's this? Submitted June 26, 2003 Accepted November 3, 2003 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* JBG Cancer Center, University of Louisville, Louisville, KY, USA Canadian Blood Services, University of Alberta, Edmonton, AB, Canada Institute of Molecular Medicine, University of Texas, Houston, TX, USA * Corresponding author; email: mzrata01{at}louisville.edu. The mechanisms regulating the homing/mobilization of hematopoietic stem/progenitor cells (HSPC) are not fully understood. In previous studies it was shown that the complement C3 activation peptide, C3a, sensitizes responses of HSPC to stromal-derived factor (SDF)-1. In this study, mobilization was induced with G-CSF in both C3-deficient (C3-/-) and C3a receptor-deficient (C3aR-/-) mice as well as in normal mice in the presence or absence of a C3aR antagonist, SB 290157. The data indicated: i) significantly increased G-CSF-induced mobilization in C3-/- and C3aR-/- mice as compared to wild-type mice, ii) significantly enhanced G-CSF-induced mobilization in wild-type (but not in C3-/- or C3aR-/-) mice treated with SB 290157, iii) deposition of C3b/iC3b fragments onto the viable bone marrow cells of G-CSF-treated mice. Accordingly it is hypothesized that C3 is activated in mobilized marrow into C3a and C3b, and that the C3a-C3aR axis plays an important and novel role in retention of HSPC (thereby counteracting mobilization) by increasing their responsiveness to SDF-1 whose concentration is reduced in marrow during mobilization. Thus, the C3a-C3aR axis may prevent an uncontrolled release of HSPC into peripheral blood. These data further suggest that SB 290157 could be developed as a drug to mobilize HSPC 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. 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