Functional receptor for C3a anaphylatoxin is expressed by normal hematopoietic stem/progenitor cells, and C3a enhances their homing-related responses to SDF-1

Blood. 2003 May 15;101(10):3784-93. doi: 10.1182/blood-2002-10-3233. Epub 2003 Jan 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, CD / analysis
  • Antigens, CD34 / analysis
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / physiology*
  • Cell Adhesion
  • Cell Line
  • Chemokine CXCL12
  • Chemokines, CXC / physiology*
  • Chemotaxis / drug effects
  • Chemotaxis / physiology*
  • Complement C3a / pharmacology*
  • Enzyme-Linked Immunosorbent Assay
  • Fibroblasts / cytology
  • Fibroblasts / physiology
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / physiology*
  • Humans
  • Jurkat Cells
  • Macrophage-1 Antigen / genetics*
  • Membrane Proteins*
  • Receptors, Complement / genetics*
  • Recombinant Proteins / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stromal Cells / cytology
  • Stromal Cells / physiology*
  • Vascular Cell Adhesion Molecule-1 / physiology


  • Antigens, CD
  • Antigens, CD34
  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines, CXC
  • Macrophage-1 Antigen
  • Membrane Proteins
  • Receptors, Complement
  • Recombinant Proteins
  • Vascular Cell Adhesion Molecule-1
  • complement C3a receptor
  • Complement C3a