Advertisement

Innate Immunity as Orchestrator of Bone Marrow Homing for Hematopoietic Stem/Progenitor Cells

  • Mariusz Z. RatajczakEmail author
  • ChiHwa Kim
  • Janina Ratajczak
  • Anna Janowska-Wieczorek
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 735)

Abstract

The first step that precedes hematopoietic transplantation is elimination of pathological hematopoiesis by administration of myeloablative doses of radiochemotherapy. This eliminates hematolymphopoietic cells and at the same time damages hematopoietic microenvironment in bone marrow (BM). The damage of BM tissue leads to activation of complement cascade (CC), and bioactive CC cleavage fragments modulate several steps of BM recovery after transplantation of hematopoietic stem progenitor cells (HSPCs). Accordingly, C3 cleavage fragments (soluble C3a/desArgC3a and solid phase iC3b) and generation of soluble form of C5b-C9 also known as membrane attack complex (MAC) as well as release of antimicrobial cationic peptides from stromal cells (cathelicidin or LL-37 and β-2 defensin) promote homing of HSPCs. To support this, C3 cleavage fragments and antimicrobial cationic peptides increase homing responsiveness of transplanted HSPCs to stroma-derived factor-1 (SDF-1) gradient. Furthermore, damaged BM cells release several other chemoattractants for HSPCs such as bioactive lipids sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P) and chemotactic purines (ATP and UTP). In this chapter, we will discuss the current view on homing of transplanted HSPCs into BM that in addition to SDF-1 is orchestrated by CC, antimicrobial cationic peptides, and several other prohoming factors. We also propose modulation of CC as a novel strategy to optimize/accelerate homing of HSPCs.

Keywords

Lipid Raft Bone Marrow Stromal Cell Membrane Attack Complex Complement Cascade Bone Marrow Microenvironment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was supported by NIH R01 DK074720 and Stella and Henry Hoenig Endowment to MZR.

References

  1. Arana L, Gangoiti P, Ouro A, Trueba M, Gómez-Muñoz A (2010) Ceramide and ceramide 1-phosphate in health and disease. Lipids Health Dis 9:15–26CrossRefGoogle Scholar
  2. Badea T, Niculescu F, Soane L, Fosbrink M, Sorana H, Rus V, Shin ML, Rus H (2002) RGC-32 increases p34CDC2 kinase activity and entry of aortic smooth muscle cells into S-phase. J Biol Chem 277:502–508CrossRefGoogle Scholar
  3. Bengtsson NE, Kim S, Lin L, Walter GA, Scott EW (2011) Ultra-high-field MRI real-time imaging of HSC engraftment of the bone marrow niche. Leukemia 25:1223–1231CrossRefGoogle Scholar
  4. Borlongan CV (2011) Bone marrow stem cell mobilization in stroke: a ‘bonehead’ may be good after all! Leukemia 25:1674–1686CrossRefGoogle Scholar
  5. Bucki R, Leszczyn’ska K, Namiot A, Sokolowski W (2010) Cathelicidin LL-37: a multitask antimicrobial peptide. Arch Immunol Ther Exp 58:15–25CrossRefGoogle Scholar
  6. Cancelas JA, Lee AW, Prabhakar R, Stringer KF, Zheng Y, Williams DA (2005) Rac GTPases differentially integrate signals regulating hematopoietic stem cell localization. Nat Med 11:886–891CrossRefGoogle Scholar
  7. Christopherson KW II, Hangoc G, Mantel CR, Broxmeyer HE (2004) Modulation of hematopoietic stem cell homing and engraftment by CD26. Science 305:1000–1003CrossRefGoogle Scholar
  8. Ciornei CD, Sigurdardottir T, Schmidtchen A, Bodelsson M (2005) Antimicrobial and chemoattractant activity, lipopolysaccharide neutralization, cytotoxicity, and inhibition by serum of analogs of human cathelicidin LL-37. Antimicrob Agents Chemother 49:2845–2850CrossRefGoogle Scholar
  9. Danet GH, Luongo JL, Butler G, Lu MM, Tenner AJ, Simon MC, Bonnet DA (2002) C1qRp defines a new human stem cell population with hematopoietic and hepatic potential. Proc Natl Acad Sci 99:10441–10445CrossRefGoogle Scholar
  10. Dar A, Kollet O, Lapidot T (2006) Mutual, reciprocal SDF-1/CXCR4 interactions between hematopoietic and bone marrow stromal cells regulate human stem cell migration and development in NOD/SCID chimeric mice. Exp Hematol 34:967–975CrossRefGoogle Scholar
  11. Dashiell SM, Rus H, Koski CL (2000) Terminal complement complexes concomitantly stimulate proliferation and rescue of Schwann cells from apoptosis. Glia 30:187–198CrossRefGoogle Scholar
  12. DiScipio RG, Schraufstatter IU, Sikora L, Zuraw BL, Sriramarao P (2006) C5a mediates secretion and activation of matrix metalloproteinase 9 from human eosinophils and neutrophils. Int Immunopharmacol 6:1109–1118CrossRefGoogle Scholar
  13. Doan PL, Chute JP (2011) The vascular niche: home for normal and malignant hematopoietic stem cells. Leukemia. doi: 10.1038/leu.2011.236
  14. Filippi MD, Harris CE, Meller J, Gu Y, Zheng Y, Williams DA (2004) Localization of Rac2 via the C terminus and aspartic acid 150 specifies superoxide generation, actin polarity and chemotaxis in neutrophils. Nat Immunol 5:744–751CrossRefGoogle Scholar
  15. Fyrst H, Saba JD (2010) An update on sphingosine-1-phosphate and other sphingolipid mediators. Nat Chem Biol 6:489–497CrossRefGoogle Scholar
  16. Ganz T (2003) Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol 3:710–720CrossRefGoogle Scholar
  17. Gómez-Moutón C, Lacalle RA, Mira E, Jiménez-Baranda S, Barber DF, Carrera AC, Martínez-A C, Mañes S (2004) Dynamic redistribution of raft domains as an organizing platform for signaling during cell chemotaxis. J Cell Biol 164:759–768CrossRefGoogle Scholar
  18. Granado MH, Gangoiti P, Ouro A, Arana L, Gonzalez M, Trueba M, Gómez-Muñoz A (2009) Ceramide 1-phosphate (C1P) promotes cell migration involvement of a specific C1P receptor. Cell Signal 21:405–412CrossRefGoogle Scholar
  19. Gu Y, Filippi MD, Cancelas JA, Siefring JE, Williams EP, Jasti AC, Harris CE, Lee AW, Prabhakar R, Atkinson SJ, Kwiatkowski DJ, Williams DA (2003) Hematopoietic cell regulation by Rac1 and Rac2 guanosine triphosphatases. Science 302:445–449CrossRefGoogle Scholar
  20. Guan JL (2004) Cell biology: integrins, rafts, Rac, and Rho. Science 302:773–774CrossRefGoogle Scholar
  21. Hoggatt J, Pelus LM (2010) Eicosanoid regulation of hematopoiesis and hematopoietic stem and progenitor trafficking. Leukemia 24:1993–2002CrossRefGoogle Scholar
  22. Hoggatt J, Singh P, Sampath J, Pelus LM (2009) Prostaglandin E2 enhances hematopoietic stem cell homing, survival, and proliferation. Blood 113:5444–5455CrossRefGoogle Scholar
  23. Jalili A, Shirvaikar N, Marquez-Curtis LA, Turner AR, Janowska-Wieczorek A (2009) The HGF/c-Met axis synergizes with G-CSF in the mobilization of hematopoietic stem/progenitor cells. Stem Cells Dev 19:1143–1151CrossRefGoogle Scholar
  24. Jalili A, Shirvaikar N, Marquez-Curtis L, Qui Y, Korol C, Lee H, Turner AR, Ratajczak MZ, Janowska-Wieczorek A (2010a) Fifth complement cascade protein (C5) cleavage fragments disrupt the SDF-1/CXCR4 axis: further evidence that innate immunity orchestrates the mobilization of hematopoietic stem/progenitor cells. Exp Hematol 38:321–332CrossRefGoogle Scholar
  25. Jalili A, Marquez-Curtis L, Shirvaikar N, Wysoczynski M, Ratajczak MZ, Janowska-Wieczorek A (2010b) Complement C1q enhances homing-related responses of hematopoietic stem/progenitor cells. Transfusion 50:2002–2010CrossRefGoogle Scholar
  26. Junger WG (2008) Purinergic regulation of neutrophil chemotaxis. Cell Mol Life Sci 65:2528–2540CrossRefGoogle Scholar
  27. Kim CH, Wu W, Wysoczynski M, Abdel-Latif A, Sunkara M, Morris A, Kucia M, Ratajczak J, Ratajczak MZ (2011a) Conditioning for hematopoietic transplantation activates the complement cascade and induces a proteolytic environment in bone marrow: a novel role for bioactive lipids and soluble C5b-C9 as homing factors. Leukemia. doi: 10.1038/leu.2011.185
  28. Kim CH, Liu R, Kucia M, Ratajczak MZ (2011b) New evidence that the bioactive lipid ceramide-1-phosphate (C1P) is a potent chemoattractant for mesenchymal stromal cells (MSC), endothelial progenitor cells (EPCs) and very small embryonic-like stem cells (VSELs), demonstrating its potential involvement in tissue/organ repair and angiogenesis. 2011 American Society of Hematology meeting. Abstract # 2387Google Scholar
  29. Kronlage M, Song J, Sorokin L, Isfort K, Schwerdtle T, Leipziger J, Robaye B, Conley PB, Kim HC, Sargin S, Schön P, Schwab A, Hanley PJ (2010) Autocrine purinergic receptor signaling is essential for macrophage chemotaxis. Sci Signal 3:ra55CrossRefGoogle Scholar
  30. Lamour NF, Stahelin RV, Wijesinghe DS, Maceyka M, Wang E, Allegood JC, Merrill AH Jr, Cho W, Chalfant CE (2007) Ceramide kinase uses ceramide provided by ceramide transport protein: localization to organelles of eicosanoid synthesis. J Lipid Res 48:1293–1304CrossRefGoogle Scholar
  31. Lapidot T, Dar A, Kollet O (2005) How do stem cells find their way home? Blood 106:1901–1910CrossRefGoogle Scholar
  32. Lee H, Ratajczak MZ (2009) Innate immunity: a key player in the mobilization of hematopoietic stem/progenitor cells. Arch Immunol Ther Exp (Warsz) 57:269–278CrossRefGoogle Scholar
  33. Lee HM, Wu W, Wysoczynski M, Liu R, Zuba-Surma EK, Kucia M, Ratajczak J, Ratajczak MZ (2009) Impaired mobilization of hematopoietic stem/progenitor cells in C5-deficient mice supports the pivotal involvement of innate immunity in this process and reveals novel promobilization effects of granulocytes. Leukemia 23:2052–2062CrossRefGoogle Scholar
  34. Lee HM, Wysoczynski M, Liu R, Shin DM, Kucia M, Botto M, Ratajczak J, Ratajczak MZ (2010) Mobilization studies in complement-deficient mice reveal that optimal AMD3100 mobilization of hematopoietic stem cells depends on complement cascade activation by AMD3100-stimulated granulocytes. Leukemia 24:573–582CrossRefGoogle Scholar
  35. Levesque JP, Takamatsu Y, Nilsson SK, Haylock DN, Simmons PJ (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 98:1289–1297CrossRefGoogle Scholar
  36. Levesque JP, Hendy J, Takamatsu Y, Simmons PJ, Bendall LJ (2003) Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by GCSF or cyclophosphamide. J Clin Invest 111:187–196CrossRefGoogle Scholar
  37. Levesque JP, Helwani FM, Winkler IG (2010) The endosteal ‘osteoblastic’ niche and its role in hematopoietic stem cell homing and mobilization. Leukemia 24:1979–1992CrossRefGoogle Scholar
  38. Ma Q, Jones D, Springer TA (1999) The chemokine receptor CXCR4 is required for the retention of B lineage and granulocytic precursors within the bone marrow microenvironment. Immunity 10:463–471CrossRefGoogle Scholar
  39. Marquez-Curtis LA, Turner AR, Sridharan S, Ratajczak MZ, Janowska-Wieczorek A (2011) The ins and outs of hematopoietic stem cells: studies to improve transplantation outcomes. Stem Cell Rev 7:590–607CrossRefGoogle Scholar
  40. Mitsutake S, Kim TJ, Inagaki Y, Kato M, Yamashita T, Igarashi Y (2004) Ceramide kinase is a mediator of calcium-dependent degranulation in mast cells. J Biol Chem 279:17570–17577CrossRefGoogle Scholar
  41. Nguyen DH, Taub D (2002) CXCR4 function requires membrane cholesterol: implications for HIV infection. J Immunol 168:4121–4126CrossRefGoogle Scholar
  42. Niculescu F, Soane L, Badea T, Shin M, Rus H (1999a) Tyrosine phosphorylation and activation of Janus kinase 1 and STAT3 by sublytic C5b-9 complement complex in aortic endothelial cells. Immunopharmacology 42:187–193CrossRefGoogle Scholar
  43. Niculescu F, Badea T, Rus H (1999b) Sublytic C5b-9 induces proliferation of human aortic smooth muscle cells: role of mitogen activated protein kinase and phosphatidylinositol 3-kinase. Atherosclerosis 142:47–56CrossRefGoogle Scholar
  44. Ohinata K, Takagi K, Biyajima K, Kaneko K, Miyamoto C, Asakawa A, Eguchi N, Urade Y, Inui A, Yoshikawa M (2009) Complement C5a stimulates food intake via a prostaglandin D(2)- and neuropeptide Y-dependent mechanism in mice. Prostaglandins Other Lipid Mediat 90:81–84CrossRefGoogle Scholar
  45. Ohkawa R, Nakamura K, Okubo S, Hosogaya S, Ozaki Y, Tozuka M, Osima N, Yokota H, Ikeda H, Yatomi Y (2008) Plasma sphingosine-1-phosphate measurement in healthy subjects: close correlation with red blood cell parameters. Ann Clin Biochem 45:356–363CrossRefGoogle Scholar
  46. Onai N, Zhang YY, Yoneyama H, Kitamura T, Ishikawa S, Matsushima K (2000) Impairment of lymphopoiesis and myelopoiesis in mice reconstituted with bone marrow-hematopoietic progenitor cells expressing SDF-1-intrakine. Blood 96:2074–2080PubMedGoogle Scholar
  47. Peled A, Grabovsky V, Habler L, Sandbank J, Arenzana-Seisdedos F, Petit I, Ben-Hur H, Lapidot T, Alon R (1999) The chemokine SDF-1 stimulates integrin-mediated arrest of CD34+ cells on vascular endothelium under shear flow. J Clin Invest 104:1199–1211CrossRefGoogle Scholar
  48. Pelus LM, Bian H, King AG, Fukuda S (2004) Neutrophil-derived MMP-9 mediates synergistic mobilization of hematopoietic stem and progenitor cells by the combination of G-CSF and the chemokines GRObeta/CXCL2 and GRObetaT/CXCL2delta4. Blood 103:110–119CrossRefGoogle Scholar
  49. Pitchford SC, Furze RC, Jones CP, Wengner AM, Rankin SM (2009) Differential mobilization of subsets of progenitor cells from the bone marrow. Cell Stem Cell 4:62–72CrossRefGoogle Scholar
  50. Ratajczak MZ (2010) Spotlight series on stem cell mobilization: many hands on the ball, but who is the quarterback? Leukemia 24:1665–1666CrossRefGoogle Scholar
  51. Ratajczak MZ, Reca R, Wysoczynski M, Kucia M, Baran JT, Allendorf DJ, Ratajczak J, Ross GD (2004a) Transplantation studies in C3-deficient animals reveal a novel role of the third complement component (C3) in engraftment of bone marrow cells. Leukemia 18:1482–1490CrossRefGoogle Scholar
  52. Ratajczak J, Reca R, Kucia M, Majka M, Allendorf DJ, Baran JT, Janowska-Wieczorek A, Wetsel RA, Ross GD, Ratajczak MZ (2004b) 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 103:2071–2078CrossRefGoogle Scholar
  53. Ratajczak MZ, Reca R, Wysoczynski M, Yan J, Ratajczak J (2006) Modulation of the SDF-1-CXCR4 axis by the third complement component (C3) – implications for trafficking of CXCR4+ stem cells. Exp Hematol 34:986–995CrossRefGoogle Scholar
  54. Ratajczak MZ, Lee H, Wysoczynski M, Wan W, Marlicz W, Laughlin MJ, Kucia M, Janowska-Wieczorek A, Ratajczak J (2010a) Novel insight into stem cell mobilization-plasma sphingosine-1-phosphate is a major chemoattractant that directs the egress of hematopoietic stem progenitor cells from the bone marrow and its level in peripheral blood increases during mobilization due to activation of complement cascade/membrane attack complex. Leukemia 24:976–985CrossRefGoogle Scholar
  55. Ratajczak MZ, Kim CH, Wojakowski W, Janowska-Wieczorek A, Kucia M, Ratajczak J (2010b) Innate immunity as orchestrator of stem cell mobilization. Leukemia 24:1667–1675CrossRefGoogle Scholar
  56. Ratajczak MZ, Kim CH, Abdel-Latif A, Schneider G, Kucia M, Morris AJ, Laughlin MJ, Ratajczak J (2011) A novel perspective on stem cell homing and mobilization: review on bioactive lipids as potent chemoattractants and cationic peptides as underappreciated modulators of responsiveness to SDF-1 gradients. Leukemia. doi: 10.1038/leu.2011.242
  57. Ratajczak MZ, Kim CH, Wu W, Shin DM, Bryndza E, Kucia M, Ratajczak J (2012) The role of innate immunity in trafficking of hematopoietic stem cells – an emerging link between activation of complement cascade and chemotactic gradients of bioactive sphingolipids. Adv Exp Med Biol 946:37–54CrossRefGoogle Scholar
  58. Reca R, Mastellos D, Majka M, Marquez L, Ratajczak J, Franchini S, Glodek A, Honczarenko M, Spruce LA, Janowska-Wieczorek A, Lambris JD, Ratajczak MZ (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 101:3784–3793CrossRefGoogle Scholar
  59. Reca R, Cramer D, Yan J, Laughlin MJ, Janowska-Wieczorek A, Ratajczak J, Ratajczak MZ (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 25:3093–3100CrossRefGoogle Scholar
  60. Rettig MP, Ansstas G, Dipersio JF (2011) Mobilization of hematopoietic stem and progenitor cells using inhibitors of CXCR4 and VLA-4. Leukemia. doi: 10.1038/leu.2011.197
  61. Rossi L, Manfredini R, Bertolini F, Ferrari D, Fogli M, Zini R, Salati S, Salvestrini V, Gulinelli S, Adinolfi E, Ferrari S, Di Virgilio F, Baccarani M, Lemoli RM (2007) The extracellular nucleotide UTP is a potent inducer of hematopoietic stem cell migration. Blood 109:533–542CrossRefGoogle Scholar
  62. Rus HG, Niculescu F, Shin ML (1996) Sublytic complement attack induces cell cycle in oligodendrocytes. J Immunol 156:4892–4900PubMedGoogle Scholar
  63. Shirvaikar N, Marquez-Curtis LA, Ratajczak MZ, Janowska-Wieczorek A (2011) Hyaluronic acid and thrombin upregulate MT1-MMP through PI3K and Rac-1 signaling and prime the homing-related responses of cord blood hematopoietic stem/progenitor cells. Stem Cells Dev 20:19–30CrossRefGoogle Scholar
  64. Speidl WS, Kastl SP, Hutter R, Katsaros KM, Kaun C, Bauriedel G, Maurer G, Huber K, Badimon JJ, Wojta J (2011) The complement component C5a is present in human coronary lesions in vivo and induces the expression of MMP-1 and MMP-9 in human macrophages in vitro. FASEB J 25:35–44CrossRefGoogle Scholar
  65. Sugita K, Kabashima K, Sakabe J, Yoshiki R, Tanizaki H, Tokura Y (2010) FTY720 regulates bone marrow egress of eosinophils and modulates late-phase skin reaction in mice. Am J Pathol 177:1881–1887CrossRefGoogle Scholar
  66. Taichman RS (2005) Blood and bone: two tissues whose fates are intertwined to create the hematopoietic stem-cell niche. Blood 105:2631–2639CrossRefGoogle Scholar
  67. Tegla CA, Cudrici C, Patel S, Trippe R 3rd, Rus V, Niculescu F, Rus H (2011) Membrane attack by complement: the assembly and biology of terminal complement complexes. Immunol Res 51:45–60CrossRefGoogle Scholar
  68. Vagima Y, Avigdor A, Goichberg P, Shivtiel S, Tesio M, Kalinkovich A, Golan K, Dar A, Kollet O, Petit I, Perl O, Rosenthal E, Resnick I, Hardan I, Gellman YN, Naor D, Nagler A, Lapidot T (2009) MT1-MMP and RECK are involved in human CD34+ progenitor cell retention, egress, and mobilization. J Clin Invest 119:492–503CrossRefGoogle Scholar
  69. Wojakowski W, Landmesser U, Bachowski R, Jadczyk T, Tendera M (2011) Mobilization of stem and progenitor cells in cardiovascular diseases. Leukemia. doi: 10.1038/leu.2011.184
  70. Wu W, Kim CH, Liu R, Kucia M, Marlicz W, Greco N, Ratajczak J, Laughlin MJ, Ratajczak MZ (2011) The bone marrow-expressed antimicrobial cationic peptide LL-37 enhances the responsiveness of hematopoietic stem progenitor cells to an SDF-1 gradient and accelerates their engraftment after transplantation. Leukemia. doi: 10.1038/leu.2011.252
  71. Wysoczynski M, Reca R, Ratajczak J, Kucia M, Shirvaikar N, Honczarenko M, Mills M, Wanzeck J, Janowska-Wieczorek A, Ratajczak MZ (2005) Incorporation of CXCR4 into membrane lipid rafts primes homing-related responses of hematopoietic stem/progenitor cells to an SDF-1 gradient. Blood 105:40–48CrossRefGoogle Scholar
  72. Wysoczynski M, Reca R, Lee H, Wu W, Ratajczak J, Ratajczak MZ (2009) Defective engraftment of C3aR−/− hematopoietic stem progenitor cells shows a novel role of the C3a-C3aR axis in bone marrow homing. Leukemia 23:1455–1461CrossRefGoogle Scholar
  73. Yang FC, Atkinson SJ, Gu Y, Borneo JB, Roberts AW, Zheng Y, Pennington J, Williams DA (2001) GTPases control hematopoietic stem cell shape, adhesion, migration, and mobilization. Proc Natl Acad Sci 98:5614–5618CrossRefGoogle Scholar
  74. Zughaier SM, Svoboda P, Pohl J, Stephens DS, Shafer WM (2010) The human host defense peptide LL-37 interacts with Neisseria meningitidis capsular polysaccharides and inhibits inflammatory mediators release. PLoS One 5:e13627CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Mariusz Z. Ratajczak
    • 1
    Email author
  • ChiHwa Kim
    • 1
  • Janina Ratajczak
    • 1
  • Anna Janowska-Wieczorek
    • 2
  1. 1.Stem Cell Biology Program at the James Graham Brown Cancer CenterUniversity of LouisvilleLouisvilleUSA
  2. 2.Department of MedicineUniversity of AlbertaEdmontonCanada

Personalised recommendations