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Prepublished online as a Blood First Edition Paper on January 2, 2003; DOI 10.1182/blood-2002-10-3233. This Article Full Text (PDF) All Versions of this Article: 2002-10-3233v1 101/10/3784    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 Reca, R. Articles by Ratajczak, M. Z Search for Related Content PubMed PubMed Citation Articles by Reca, R. Articles by Ratajczak, M. Z Social Bookmarking                   What's this? Submitted October 25, 2002 Accepted December 30, 2002 Functional receptor for C3a anaphylatoxin is expressed by normal hematopoietic stem/progenitor cells, and C3a enhances their homing-related responses to SDF-1 Ryan Reca, Dimitrios Mastellos, Marcin Majka, Leah Marquez, Janina Ratajczak, Silvia Franchini, Aleksandra Glodek, Marek Honczarenko, Lynn A Spruce, Anna Janowska-Wieczorek, John D Lambris, and Mariusz Z Ratajczak* Stem Cell Biology Program, University of Louisville, Louisville, KY, USA Pathology & Lab. Medicine, University of Pennsylvania, Philadelphia, PA, USA Joint Program in Transfusion Medicine, Harvard Medical School, Boston, MA, USA Medicine, University of Alberta, Edmonton, Alberta, Canada * Corresponding author; email: mzrata01{at}louisville.edu. Complement has recently been implicated in developmental pathways and non-inflammatory processes. The expression of various complement components and receptors has been shown in a wide range of circulating myeloid and lymphoid cells but their role in normal hematopoiesis and stem cell homing has not yet been investigated. We report that normal human CD34+ cells and lineage-differentiated hematopoietic progenitors express the complement anaphylatoxin C3a receptor (C3aR) and respond to C3a. Moreover, C3a, but not the biologically inactive desArg-C3a, induces calcium flux in these cells. Furthermore, we found that C3 is secreted by bone marrow stroma and that, although C3a does not influence directly the proliferation/survival of hematopoietic progenitors, it potentiates the stromal cell-derived factor (SDF-1)-dependent chemotaxis of human CD34+ cells and lineage-committed myeloid, erythroid and megakaryocytic progenitors, primes SDF-1-dependent trans-Matrigel migration and stimulates matrix metalloproteinase-9 secretion and VLA-4 mediated adhesion to VCAM-1. Furthermore, we found that murine Sca-1+ cells primed by C3a engrafted faster in lethally irradiated animals. These results indicate that normal human hematopoietic stem and progenitor cells express functional C3aR and that the C3aR-C3a axis sensitizes the responses of these cells to SDF-1 and thus may be involved in promoting their homing into the bone marrow via crosstalk with the SDF-CXCR4 signaling axis. C3a is the first positive regulator of this axis to be identified. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: V. Enzmann, E. Yolcu, H. J. Kaplan, and S. T. Ildstad Stem Cells as Tools in Regenerative Therapy for Retinal Degeneration Arch Ophthalmol, April 1, 2009; 127(4): 563 - 571. [Abstract] [Full Text] [PDF] W. Wu, H. Lee, M. Wysoczynski, M. Kucia, J. Ratajczak, and M. 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