Skip to main content

Advertisement

SpringerLink
Log in

Innate immunity: a key player in the mobilization of hematopoietic stem/progenitor cells

  • Review
  • Published:
Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

The mobilization of hematopoietic stem/progenitor cells (HSPCs) from bone marrow into peripheral blood (PB) is still not fully understood. Different chemokines, cytokines, growth factors, and neurotransmitters have been described that facilitate this process. However, mounting evidence suggests that mobilization of HSPCs is a part of the immune response and is mediated by innate immunity. We discuss evidence showing that complement system cleavage fragments play a crucial role in both the retention and mobilization of HSPCs by modulating their responsiveness to stromal-derived growth factor-1 (SDF-1) gradient (by C3-derived anaphylatoxins) and by modulating the release of granulocytes into PB that subsequently facilitate the egress of HSPCs (by C5-derived anaphylatoxins).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Andrews RG, Briddell RA, Knitter GH et al (1994) In vivo synergy between recombinant human stem cell factor and recombinant human granulocyte colony-stimulating factor in baboons enhanced circulation of progenitor cells. Blood 84: 800–810

    PubMed  CAS  Google Scholar 

  • Bellucci R, De Propris MS, Buccisano F et al (1999) Modulation of VLA-4 and L-selectin expression on normal CD34+ cells during mobilization with G-CSF. Bone Marrow Transplant 23: 1–8

    Article  PubMed  CAS  Google Scholar 

  • Bensinger W, Dipersio JF, McCarty JM (2009) Improving stem cell mobilization strategies: future directions. Bone Marrow Transplant 43: 181–195

    Article  PubMed  CAS  Google Scholar 

  • Bönig H, Burdach S, Göbel U et al (2001) Growth factors and hemostasis: differential effects of GM-CSF and G-CSF on coagulation activation – laboratory and clinical evidence. Ann Hematol 80: 525–530

    Article  PubMed  Google Scholar 

  • Cain SA, Monk PN (2002) The orphan receptor C5L2 has high affinity binding sites for complement fragments C5a and C5a des-Arg(74). J Biol Chem 277: 7165–7169

    Article  PubMed  CAS  Google Scholar 

  • Campbell FR (1986) Ultrastructural studies of intercellular contacts (junctions) in bone marrow. Scan Electron Microsc Pt2: 621–629

    Google Scholar 

  • Canales MA, Arrieta R, Gomez-Rioja R et al (2002) Induction of a hypercoagulability state and endothelial cell activation by granulocyte colony-stimulating factor in peripheral blood stem cell donors. J Hematother Stem Cell Res 11: 675–681

    Article  PubMed  Google Scholar 

  • Cramer DE, Wagner S, Li B et al (2008) Mobilization of hematopoietic progenitor cells by yeast-derived beta-glucan requires activation of matrix metalloproteinase-9. Stem Cells 26: 1231–1240

    Article  PubMed  CAS  Google Scholar 

  • Fruehauf S, Seeger T, Topaly J (2005) Innovative strategies for PBPC mobilization. Cytotherapy 7: 438–446

    Article  PubMed  CAS  Google Scholar 

  • Glaspy JA, Shpall EJ, LeMaistre CF et al (1997) Peripheral blood progenitor cell mobilization using stem cell factor in combination with filgrastim in breast cancer patients. Blood 90: 2939–2951

    PubMed  CAS  Google Scholar 

  • Gómez-Moutón C, Lacalle RA, Mira E et al (2004) Dynamic redistribution of raft domains as an organizing platform for signaling during cell chemotaxis. J Cell Biol 164: 759–768

    Article  PubMed  Google Scholar 

  • Goodman JW, Hodgson GS (1962) Evidence for stem cells in the peripheral blood of mice. Blood 19: 702–714

    PubMed  CAS  Google Scholar 

  • Guan JL (2004) Cell biology. Integrins, rafts, Rac, and Rho. Science 303: 773–774

    Article  PubMed  CAS  Google Scholar 

  • Hattori K, Dias S, Heissig B et al (2001) Vascular endothelial growth factor and angiopoietin-1 stimulate postnatal hematopoiesis by recruitment of vasculogenic and hematopoietic stem cells. J Exp Med 193: 1005–1014

    Article  PubMed  CAS  Google Scholar 

  • Henon PR, Liang H, Beck-Wirth G et al (1992) Comparison of hematopoietic and immune recovery after autologous bone marrow or blood stem cell transplants. Bone Marrow Transplant 9: 285–291

    PubMed  CAS  Google Scholar 

  • Huber-Lang M, Sarma JV, Zetoune FS et al (2006) Generation of C5a in the absence of C3: a new complement activation pathway. Nat Med 12: 682–687

    Article  PubMed  CAS  Google Scholar 

  • Kassirer M, Zeltser D, Gluzman B et al (1999) The appearance of L-selectin(low) polymorphonuclear leukocytes in the circulating pool of peripheral blood during myocardial infarction correlates with neutrophilia and with the size of the infarct. Clin Cardiol 22: 721–726

    Article  PubMed  CAS  Google Scholar 

  • King AG, Horowitz D, Dillon SB et al (2001) Rapid mobilization of murine hematopoietic stem cells with enhanced engraftment properties and evaluation of hematopoietic progenitor cell mobilization in rhesus monkeys by a single injection of SB-251353, a specific truncated form of the human CXC chemokine GRObeta. Blood 97: 1534–1542

    Article  PubMed  CAS  Google Scholar 

  • Kyne L, Hausdorff JM, Knight E et al (2000) Neutrophilia and congestive heart failure after acute myocardial infarction. Am Heart J 139(1 Pt 1): 94–100

    Article  PubMed  CAS  Google Scholar 

  • Lapidot T, Dar A, Kollet O (2005) How do stem cells find their way home?. Blood 106: 1901–1910

    Article  PubMed  CAS  Google Scholar 

  • Lapidot T, Petit I (2002) Current understanding of stem cell mobilization: The roles of chemokines, proteolytic enzymes, adhesion molecules, cytokines, and stromal cells. Exp Hematol 30: 973–981

    Article  PubMed  CAS  Google Scholar 

  • Laterveer L, Lindley IJ, Hamilton MS et al (1995) Interleukin-8 induces rapid mobilization of hematopoietic stem cells with radioprotective capacity and long-term myelolymphoid repopulating ability. Blood 85: 2269–2275

    PubMed  CAS  Google Scholar 

  • Lévesque JP, Hendy J, Takamatsu Y et al (2003a) Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by GCSF or cyclophosphamide. J Clin Invest 111: 187–196

    PubMed  Google Scholar 

  • Lévesque JP, Hendy J, Winkler IG et al (2003b) Granulocyte colony-stimulating factor induces the release in the bone marrow of proteases that cleave c-KIT receptor (CD117) from the surface of hematopoietic progenitor cells. Exp Hematol 31: 109–117

    Article  PubMed  Google Scholar 

  • Lévesque JP, Liu F, Simmons PJ et al (2004) Characterization of hematopoietic progenitor mobilization in protease-deficient mice. Blood 104: 65–72

    Article  PubMed  Google Scholar 

  • Lévesque JP, Takamatsu Y, Nilsson SK et al (2001) Vascular cell adhesion molecule-1 (CD106) is cleaved by neutrophil proteases in the bone marrow following hematopoietic progenitor cell mobilization by granulocyte colony-stimulating factor.. Blood 98: 1289–1297

    Article  PubMed  Google Scholar 

  • Liles WC, Broxmeyer HE, Rodger E et al (2003) Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD3100, a CXCR4 antagonist. Blood 102: 2728–2730

    Article  PubMed  CAS  Google Scholar 

  • Markiewski MM, Lambris JD (2007) The role of complement in inflammatory diseases from behind the scenes into the spotlight.. Am J Pathol 171: 715–727

    Article  PubMed  CAS  Google Scholar 

  • Massberg S, Schaerli P, Knezevic-Maramica I et al (2007) Immunosurveillance by hematopoietic progenitor cells trafficking through blood, lymph, and peripheral tissues. Cell 131: 994–1008

    Article  PubMed  CAS  Google Scholar 

  • Mohle R, Rafii S, Moore MA (1998) The role of endothelium in the regulation of hematopoietic stem cell migration. Stem Cells 16(suppl 1): 159–165

    PubMed  Google Scholar 

  • Molendijk WJ, van Oudenaren A, van Dijk H et al (1986) Complement split product C5a mediates the lipopolysaccharide- induced mobilization of CFU-s and haemopoietic progenitor cells, but not the mobilization induced by proteolytic enzymes. Cell Tissue Kinet 19: 407–417

    PubMed  CAS  Google Scholar 

  • Nagai Y, Garrett KP, Ohta S et al (2006) Toll-like receptors on hematopoietic progenitor cells stimulate innate immune system replenishment. Immunity 24: 801–812

    Article  PubMed  CAS  Google Scholar 

  • Papayannopoulou T (2004) Current mechanistic scenarios in hematopoietic stem/progenitor cell mobilization. Blood 103: 1580–1585

    Article  PubMed  CAS  Google Scholar 

  • Papayannopoulou T, Nakamoto B, Andrews RG et al (1997) In vivo effects of Flt3/Flk2 ligand on mobilization of hematopoietic progenitors in primates and potent synergistic enhancement with granulocyte colony-stimulating factor. Blood 90: 620–629

    PubMed  CAS  Google Scholar 

  • Peled A, Grabovsky V, Habler L et al (1999) The chemokine SDF-1 stimulates integrin-mediated arrest of CD34+ cells on vascular endothelium under shear flow. J Clin Invest 104: 1199–1211

    Article  PubMed  CAS  Google Scholar 

  • Petit I, Szyper-Kravitz M, Nagler A et al (2002) G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4. Nat Immunol 3: 687–694

    Article  PubMed  CAS  Google Scholar 

  • Pruijt JF, Fibbe WE, Laterveer L et al (1999) Prevention of interleukin-8-induced mobilization of hematopoietic progenitor cells in rhesus monkeys by inhibitory antibodies against the metalloproteinase gelatinase B (MMP-9). Proc Natl Acad Sci USA 96: 10863–10868

    Article  PubMed  CAS  Google Scholar 

  • Pruijt JF, Verzaal P, van Os R et al (2002) Neutrophils are indispensable for hematopoietic stem cell mobilization induced by interleukin-8 in mice. Proc Natl Acad Sci USA 99: 6228–6233

    Article  PubMed  CAS  Google Scholar 

  • Ratajczak J, Reca R, Kucia M et al (2004a) 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. Blood 103: 2071–2078

    Article  PubMed  CAS  Google Scholar 

  • Ratajczak MZ, Reca R, Wysoczynski M et al (2004b) Transplantation studies in C3-deficient animals reveal a novel role of the third complement component (C3) in engraftment of bone marrow cells. Leukemia 18: 1482–1490

    Article  PubMed  CAS  Google Scholar 

  • Ratajczak MZ, Reca R, Wysoczynski M et al (2006) Modulation of the SDF-1-CXCR4 axis by the third complement component (C3) – implications for trafficking of CXCR4+ stem cells. Exp Hematol 34: 986–995

    Article  PubMed  CAS  Google Scholar 

  • Reca R, Cramer D, Yan J et al (2007) A novel role of complement in mobilization: immunodeficient mice are poor granulocyte- colony stimulating factor mobilizers because they lack complement-activating immunoglobulins. Stem Cells 25: 3093–3100

    Article  PubMed  CAS  Google Scholar 

  • Reca R, Mastellos D, Majka M et al (2003) Functional receptor for C3a anaphylatoxin is expressed by normal hematopoietic stem/progenitor cells, and C3a enhances their homing-related responses to SDF-1. Blood 101: 3784–3793

    Article  PubMed  CAS  Google Scholar 

  • Riedemann NC, Guo RF, Ward PA (2003) A key role of C5a/C5aR activation for the development of sepsis. J Leukoc Biol 74: 966–970

    Article  PubMed  CAS  Google Scholar 

  • Sato M, Sano H, Iwaki D et al (2003) Direct binding of Toll-like receptor 2 to zymosan, and zymosan-induced NF-kappa B activation and TNF-alpha secretion are down-regulated by lung collectin surfactant protein A. J Immunol 171: 417–425

    PubMed  CAS  Google Scholar 

  • Sato N, Sawada K, Takahashi TA et al (1994) A time course study for optimal harvest of peripheral blood progenitor cells by granulocyte colony-stimulating factor in healthy volunteers. Exp Hematol 22: 973–978

    PubMed  CAS  Google Scholar 

  • Seitz G, Boehmler AM, Kanz L et al (2005) The role of sphingosine 1-phosphate receptors in the trafficking of hematopoietic progenitor cells. Ann NY Acad Sci 1044: 84–89

    Article  PubMed  CAS  Google Scholar 

  • Sekhsaria S, Fleisher TA, Vowells S et al (1996) Granulocyte colony-stimulating factor recruitment of CD34+ progenitors to peripheral blood: Impaired mobilization in chronic granulomatous disease and adenosine deaminase-deficient severe combined immunodeficiency disease patients. Blood 88: 1104–1112

    PubMed  CAS  Google Scholar 

  • Sweeney EA, Lortat-Jacob H, Priestley GV et al (2002) Sulfated polysaccharides increase plasma levels of SDF-1 in monkeys and mice: involvement in mobilization of stem/progenitor cells. Blood 99: 44–51

    Article  PubMed  CAS  Google Scholar 

  • Sweeney EA, Priestley GV, Nakamoto B et al (2000) Mobilization of stem/progenitor cells by sulfated polysaccharides does not require selectin presence. Proc Natl Acad Sci USA 97: 6544–6549

    Article  PubMed  CAS  Google Scholar 

  • Tavassoli M (1992) The role of conditioning regimens in homing of transplanted hemopoietic cells. Bone Marrow Transplant 10: 15–17

    PubMed  CAS  Google Scholar 

  • To LB, Roberts MM, Haylock DN et al (1992) Comparison of haematological recovery times and supportive care requirements of autologous recovery phase peripheral blood stem cell transplants, autologous bone marrow transplants and allogeneic bone marrow transplants. Bone Marrow Transplant 9: 277–284

    PubMed  CAS  Google Scholar 

  • Velders GA, van Os R, Hagoort H et al (2004) Reduced stem cell mobilization in mice receiving antibiotic modulation of the intestinal flora: involvement of endotoxins as cofactors in mobilization. Blood 103: 340–346

    Article  PubMed  CAS  Google Scholar 

  • Vos O, Wilschut IJ (1979) Further studies on mobilization of CFUs. Cell Tissue Kinet 12: 257–267

    PubMed  CAS  Google Scholar 

  • Winkler IG, Levesque JP (2006) Mechanisms of hematopoietic stem cell mobilization: When innate immunity assails the cells that make blood and bone. Exp Hematol 34: 996–1009

    Article  PubMed  CAS  Google Scholar 

  • Wright DE, Wagers AJ, Gulati AP et al (2001) Physiological migration of hematopoietic stem and progenitor cells. Science 294: 1933–1936

    Article  PubMed  CAS  Google Scholar 

  • Wu W, Lee H, Wysoczynski M et al (2008) 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 #67 112: 32

    Google Scholar 

  • Wysoczynski M, Reca R, Lee H et al (2009) Defective engraftment of C3aR(-/-) hematopoietic stem progenitor cells shows a novel role of the C3a-C3aR axis in bone marrow homing. Leukemia. Doi: 10.1038/leu.2009.73

  • Wysoczynski M, Reca R, Ratajczak J et al (2005) Incorporation of CXCR4 into membrane lipid rafts primes homing-related responses of hematopoietic stem cells to an SDF-1 gradient. Blood 105: 40–48

    Article  PubMed  CAS  Google Scholar 

  • Yang FC, Atkinson SJ, Gu Y et al (2001) Rac and Cdc42 GTPases control hematopoietic stem cell shape, adhesion, migration, and mobilization. Proc Natl Acad Sci USA 98: 5614–5618

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. James Graham Brown Cancer Center, Stem Cell Institute, University of Louisville, 500 Floyd St., Louisville, KY, 40202, USA

    HakMo Lee & Mariusz Z. Ratajczak MD, Ph.D. (Director and Professor)

  2. Department of Physiopathology, Pomeranian Medical University, Szczecin, Poland

    Mariusz Z. Ratajczak MD, Ph.D. (Director and Professor)

Authors
  1. HakMo Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mariusz Z. Ratajczak MD, Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mariusz Z. Ratajczak MD, Ph.D..

About this article

Cite this article

Lee, H., Ratajczak, M.Z. Innate immunity: a key player in the mobilization of hematopoietic stem/progenitor cells. Arch. Immunol. Ther. Exp. 57, 269–278 (2009). https://doi.org/10.1007/s00005-009-0037-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00005-009-0037-6

Keywords

Search

Navigation