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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 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 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 Reca, R. Articles by Ratajczak, M. Z. Search for Related Content PubMed PubMed Citation Articles by Reca, R. Articles by Ratajczak, M. Z. Related Collections Hematopoiesis and Stem Cells Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 May 2003, Vol. 101, No. 10, pp. 3784-3793 CHEMOKINES 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 From the Stem Cell Biology Program, University of Louisville, Louisville, KY; the Protein Chemistry Laboratory, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA; the Joint Program in Transfusion Medicine, Harvard Medical School, Boston, MA; Department of Transplantology, Children's Hospital, Jagiellonian University, Cracow, Poland; and the Department of Medicine, University of Alberta and Canadian Blood Services (CBS), Edmonton, AB, Canada. Complement has recently been implicated in developmental pathways and noninflammatory 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 (1) potentiates the stromal cell-derived factor 1 (SDF-1)-dependent chemotaxis of human CD34+ cells and lineage-committed myeloid, erythroid, and megakaryocytic progenitors; (2) primes SDF-1-dependent trans-Matrigel migration; and (3) stimulates matrix metalloproteinase-9 secretion and very late antigen 4 (VLA-4)-mediated adhesion to vascular cell adhesion molecule 1 (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 cross talk with the SDF-CXC chemokine receptor-4 (CXCR4) signaling axis. C3a is the first positive regulator of this axis to be identified. © 2003 by The American Society of Hematology.   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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