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Regulation of neutrophil trafficking from the bone marrow

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Abstract

Neutrophils are an essential component of the innate immune response and a major contributor to inflammation. Consequently, neutrophil homeostasis in the blood is highly regulated. Neutrophil number in the blood is determined by the balance between neutrophil production in the bone marrow and release from the bone marrow to blood with neutrophil clearance from the circulation. This review will focus on mechanisms regulating neutrophil release from the bone marrow. In particular, recent data demonstrating a central role for the chemokines CXCL12 and CXCL2 in regulating neutrophil egress from the bone marrow will be discussed.

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References

  1. Grau AJ, Boddy AW, Dukovic DA, Buggle F, Lichy C, Brandt T, Hacke W (2004) Leukocyte count as an independent predictor of recurrent ischemic events. Stroke 35(5):1147–1152

    Article  PubMed  Google Scholar 

  2. Madjid M, Awan I, Willerson JT, Casscells SW (2004) Leukocyte count and coronary heart disease: implications for risk assessment. J Am Coll Cardiol 44(10):1945–1956

    Article  PubMed  Google Scholar 

  3. Demetri GD, Griffin JD (1991) Granulocyte colony-stimulating factor and its receptor. Blood 78(11):2791–2808

    PubMed  CAS  Google Scholar 

  4. Semerad CL, Liu F, Gregory AD, Stumpf K, Link DC (2002) G-CSF is an essential regulator of neutrophil trafficking from the bone marrow to the blood. Immunity 17(4):413–423

    Article  PubMed  CAS  Google Scholar 

  5. Lieschke GJ, Grail D, Hodgson G, Metcalf D, Stanley E, Cheers C, Fowler KJ, Basu S, Zhan YF, Dunn AR (1994) Mice lacking granulocyte colony-stimulating factor have chronic neutropenia, granulocyte and macrophage progenitor cell deficiency, and impaired neutrophil mobilization. Blood 84(6):1737–1746

    PubMed  CAS  Google Scholar 

  6. Liu F, Wu HY, Wesselschmidt R, Kornaga T, Link DC (1996) Impaired production and increased apoptosis of neutrophils in granulocyte colony-stimulating factor receptor-deficient mice. Immunity 5(5):491–501

    Article  PubMed  CAS  Google Scholar 

  7. Molineux G, Migdalska A, Szmitkowski M, Zsebo K, Dexter TM (1991) The effects on hematopoiesis of recombinant stem cell factor (ligand for c-kit) administered in vivo to mice either alone or in combination with granulocyte colony-stimulating factor. Blood 78(4):961–966

    PubMed  CAS  Google Scholar 

  8. Seymour JF, Lieschke GJ, Grail D, Quilici C, Hodgson G, Dunn AR (1997) Mice lacking both granulocyte colony-stimulating factor (CSF) and granulocyte-macrophage CSF have impaired reproductive capacity, perturbed neonatal granulopoiesis, lung disease, amyloidosis, and reduced long-term survival. Blood 90(8):3037–3049

    PubMed  CAS  Google Scholar 

  9. Liu F, Poursine-Laurent J, Wu HY, Link DC (1997) Interleukin-6 and the granulocyte colony-stimulating factor receptor are major independent regulators of granulopoiesis in vivo but are not required for lineage commitment or terminal differentiation. Blood 90(7):2583–2590

    PubMed  CAS  Google Scholar 

  10. Rosmarin AG, Yang Z, Resendes KK (2005) Transcriptional regulation in myelopoiesis: hematopoietic fate choice, myeloid differentiation, and leukemogenesis. Exp Hematol 33(2):131–143

    Article  PubMed  CAS  Google Scholar 

  11. Cartwright GE, Athens JW, Wintrobe MM (1964) The kinetics of granulopoiesis in normal man. Blood 24:780–803

    PubMed  CAS  Google Scholar 

  12. Dancey JT, Deubelbeiss KA, Harker LA, Finch CA (1976) Neutrophil kinetics in man. J Clin Invest 58(3):705–715

    Article  PubMed  CAS  Google Scholar 

  13. Pillay J, den Braber I, Vrisekoop N, Kwast LM, de Boer RJ, Borghans JA, Tesselaar K, Koenderman L (2010) In vivo labeling with 2H2O reveals a human neutrophil lifespan of 5.4 days. Blood 116 (4):625–627

    Google Scholar 

  14. Rankin SM (2010) The bone marrow: a site of neutrophil clearance. J Leukoc Biol 88(2):241–251

    Article  PubMed  CAS  Google Scholar 

  15. Thakur ML, Lavender JP, Arnot RN, Silvester DJ, Segal AW (1977) Indium-111-labeled autologous leukocytes in man. J Nucl Med 18(10):1014–1021

    PubMed  CAS  Google Scholar 

  16. Suratt BT, Young SK, Lieber J, Nick JA, Henson PM, Worthen GS (2001) Neutrophil maturation and activation determine anatomic site of clearance from circulation. Am J Physiol Lung Cell Mol Physiol 281(4):L913–L921

    PubMed  CAS  Google Scholar 

  17. Furze RC, Rankin SM (2008) Neutrophil mobilization and clearance in the bone marrow. Immunology 125(3):281–288

    Article  PubMed  CAS  Google Scholar 

  18. Nagase H, Miyamasu M, Yamaguchi M, Imanishi M, Tsuno NH, Matsushima K, Yamamoto K, Morita Y, Hirai K (2002) Cytokine-mediated regulation of CXCR4 expression in human neutrophils. J Leukoc Biol 71(4):711–717

    PubMed  CAS  Google Scholar 

  19. Martin C, Burdon PCE, Bridger G, Gutierrez-Ramos JC, Williams TJ, Rankin SM (2003) Chemokines acting via CXCR2 and CXCR4 control the release of neutrophils from the bone marrow and their return following senescence. Immunity 19(4):583–593

    Article  PubMed  CAS  Google Scholar 

  20. Suratt BT, Petty JM, Young SK, Malcolm KC, Lieber JG, Nick JA, Gonzalo J-A, Henson PM, Worthen GS (2004) Role of the CXCR4/SDF-1 chemokine axis in circulating neutrophil homeostasis. Blood 104(2):565–571

    Article  PubMed  CAS  Google Scholar 

  21. Eash KJ, Means JM, White DW, Link DC (2009) CXCR4 is a key regulator of neutrophil release from the bone marrow under basal and stress granulopoiesis conditions. Blood 113(19):4711–4719

    Article  PubMed  CAS  Google Scholar 

  22. Campbell FR (1972) Ultrastructural studies of transmural migration of blood cells in the bone marrow of rats, mice and guinea pigs. Am J Anat 135(4):521–535

    Article  PubMed  CAS  Google Scholar 

  23. Inoue S, Osmond DG (2001) Basement membrane of mouse bone marrow sinusoids shows distinctive structure and proteoglycan composition: a high resolution ultrastructural study. Anat Rec 264(3):294–304

    Article  PubMed  CAS  Google Scholar 

  24. Burdon PCE, Martin C, Rankin SM (2008) Migration across the sinusoidal endothelium regulates neutrophil mobilization in response to ELR + CXC chemokines. Br J Haematol 142(1):100–108

    Article  PubMed  CAS  Google Scholar 

  25. Lévesque JP, Hendy J, Takamatsu Y, Williams B, Winkler IG, Simmons PJ (2002) Mobilization by either cyclophosphamide or granulocyte colony-stimulating factor transforms the bone marrow into a highly proteolytic environment. Exp Hematol 30(5):440–449

    Article  PubMed  Google Scholar 

  26. Opdenakker G, Fibbe WE, Van Damme J (1998) The molecular basis of leukocytosis. Immunol Today 19(4):182–189

    Article  PubMed  CAS  Google Scholar 

  27. Etzioni A (2009) Genetic etiologies of leukocyte adhesion defects. Curr Opin Immunol 21(5):481–486

    Article  PubMed  CAS  Google Scholar 

  28. Simmons PJ, Masinovsky B, Longenecker BM, Berenson R, Torok-Storb B, Gallatin WM (1992) Vascular cell adhesion molecule-1 expressed by bone marrow stromal cells mediates the binding of hematopoietic progenitor cells. Blood 80(2):388–395

    PubMed  CAS  Google Scholar 

  29. Schweitzer KM, Dräger AM, van der Valk P, Thijsen SF, Zevenbergen A, Theijsmeijer AP, van der Schoot CE, Langenhuijsen MM (1996) Constitutive expression of E-selectin and vascular cell adhesion molecule-1 on endothelial cells of hematopoietic tissues. Am J Pathol 148(1):165–175

    PubMed  CAS  Google Scholar 

  30. Scott LM, Priestley GV, Papayannopoulou T (2003) Deletion of alpha4 integrins from adult hematopoietic cells reveals roles in homeostasis, regeneration, and homing. Mol Cell Biol 23(24):9349–9360

    Article  PubMed  CAS  Google Scholar 

  31. Burdon PCE, Martin C, Rankin SM (2005) The CXC chemokine MIP-2 stimulates neutrophil mobilization from the rat bone marrow in a CD49d-dependent manner. Blood 105(6):2543–2548

    Article  PubMed  CAS  Google Scholar 

  32. Ley K, Laudanna C, Cybulsky MI, Nourshargh S (2007) Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol 7(9):678–689

    Article  PubMed  CAS  Google Scholar 

  33. Larangeira AP, Silva AR, Gomes RN, Penido C, Henriques MG, Castro-Faria-Neto HC, Bozza PT (2001) Mechanisms of allergen- and LPS-induced bone marrow eosinophil mobilization and eosinophil accumulation into the pleural cavity: a role for CD11b/CD18 complex. Inflamm Res 50(6):309–316

    Article  PubMed  CAS  Google Scholar 

  34. Scharffetter-Kochanek K, Lu H, Norman K, van Nood N, Munoz F, Grabbe S, McArthur M, Lorenzo I, Kaplan S, Ley K, Smith CW, Montgomery CA, Rich S, Beaude AL (1998) Spontaneous skin ulceration and defective T cell function in CD18 null mice. J Exp Med 188(1):119–131

    Article  PubMed  CAS  Google Scholar 

  35. Forlow SB, Schurr JR, Kolls JK, Bagby GJ, Schwarzenberger PO, Ley K (2001) Increased granulopoiesis through interleukin-17 and granulocyte colony-stimulating factor in leukocyte adhesion molecule-deficient mice. Blood 98(12):3309–3314

    Article  PubMed  CAS  Google Scholar 

  36. Stark MA, Huo Y, Burcin TL, Morris MA, Olson TS, Ley K (2005) Phagocytosis of apoptotic neutrophils regulates granulopoiesis via IL-23 and IL-17. Immunity 22(3):285–294

    Article  PubMed  CAS  Google Scholar 

  37. Rogowski O, Sasson Y, Kassirer M, Zeltser D, Maharshak N, Arber N, Halperin P, Serrov J, Sorkin P, Eldor A, Berliner S (1998) Down-regulation of the CD62L antigen as a possible mechanism for neutrophilia during inflammation. Br J Haematol 101(4):666–669

    Article  PubMed  CAS  Google Scholar 

  38. Kassirer M, Zeltser D, Gluzman B, Leibovitz E, Goldberg Y, Roth A, Keren G, Rotstein R, Shapira I, Arber N, Berliner AS (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(11):721–726

    Article  PubMed  CAS  Google Scholar 

  39. Robinson SD, Frenette PS, Rayburn H, Cummiskey M, Ullman-Culleré M, Wagner DD, Hynes RO (1999) Multiple, targeted deficiencies in selectins reveal a predominant role for P-selectin in leukocyte recruitment. Proc Natl Acad Sci USA 96(20):11452–11457

    Article  PubMed  CAS  Google Scholar 

  40. Arbonés ML, Ord DC, Ley K, Ratech H, Maynard-Curry C, Otten G, Capon DJ, Tedder TF (1994) Lymphocyte homing and leukocyte rolling and migration are impaired in L-selectin-deficient mice. Immunity 1(4):247–260

    Article  PubMed  Google Scholar 

  41. Heissig B, Hattori K, Dias S, Friedrich M, Ferris B, Hackett NR, Crystal RG, Besmer P, Lyden D, Moore MAS, Werb Z, Rafii S (2002) Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell 109(5):625–637

    Article  PubMed  CAS  Google Scholar 

  42. Petit I, Szyper-Kravitz M, Nagler A, Lahav M, Peled A, Habler L, Ponomaryov T, Taichman RS, Arenzana-Seisdedos F, Fujii N, Sandbank J, Zipori D, Lapidot T (2002) G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4. Nat Immunol 3(7):687–694

    Article  PubMed  CAS  Google Scholar 

  43. Lévesque J-P, Hendy J, Winkler IG, Takamatsu Y, Simmons PJ (2003) 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(2):109–117

    Article  PubMed  Google Scholar 

  44. Lévesque J-P, 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(2):187–196

    PubMed  Google Scholar 

  45. Levesque J, Liu F, Simmons PJ, Betsuyaku T, Senior RM, Pham C, Link DC (2004) Characterization of hematopoietic progenitor mobilization in protease-deficient mice. Blood 104(1):65–72

    Article  PubMed  CAS  Google Scholar 

  46. Aiuti A, Webb IJ, Bleul C, Springer T, Gutierrez-Ramos JC (1997) The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheral blood. J Exp Med 185(1):111–120

    Article  PubMed  CAS  Google Scholar 

  47. Kawabata K, Ujikawa M, Egawa T, Kawamoto H, Tachibana K, Iizasa H, Katsura Y, Kishimoto T, Nagasawa T (1999) A cell-autonomous requirement for CXCR4 in long-term lymphoid and myeloid reconstitution. Proc Natl Acad Sci USA 96(10):5663–5667

    Article  PubMed  CAS  Google Scholar 

  48. Shirozu M, Nakano T, Inazawa J, Tashiro K, Tada H, Shinohara T, Honjo T (1995) Structure and chromosomal localization of the human stromal cell-derived factor 1 (SDF1) gene. Genomics 28(3):495–500

    Article  PubMed  CAS  Google Scholar 

  49. Semerad CL, Christopher MJ, Liu F, Short B, Simmons PJ, Winkler I, Levesque J, Chappel J, Ross FP, Link DC (2005) G-CSF potently inhibits osteoblast activity and CXCL12 mRNA expression in the bone marrow. Blood 106(9):3020–3027

    Article  PubMed  CAS  Google Scholar 

  50. Ara T, Nakamura Y, Egawa T, Sugiyama T, Abe K, Kishimoto T, Matsui Y, Nagasawa T (2003) Impaired colonization of the gonads by primordial germ cells in mice lacking a chemokine, stromal cell-derived factor-1 (SDF-1). Proc Natl Acad Sci USA 100(9):5319–5323

    Article  PubMed  CAS  Google Scholar 

  51. Sugiyama T, Kohara H, Noda M, Nagasawa T (2006) Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity 25(6):977–988

    Article  PubMed  CAS  Google Scholar 

  52. Christopher MJ, Liu F, Hilton MJ, Long F, Link DC (2009) Suppression of CXCL12 production by bone marrow osteoblasts is a common and critical pathway for cytokine-induced mobilization. Blood 114(7):1331–1339

    Article  PubMed  CAS  Google Scholar 

  53. Sierro F, Biben C, Martínez-Muñoz L, Mellado M, Ransohoff RM, Li M, Woehl B, Leung H, Groom J, Batten M, Harvey RP, Martínez-A C, Mackay CR, Mackay F (2007) Disrupted cardiac development but normal hematopoiesis in mice deficient in the second CXCL12/SDF-1 receptor, CXCR7. Proc Natl Acad Sci USA 104(37):14759–14764

    Article  PubMed  CAS  Google Scholar 

  54. Berahovich RD, Zabel BA, Penfold MET, Lewén S, Wany Y, Miao Z, Gan L, Pereda J, Dias J, Slukvin II, McGrath KE, Jaen JC, Schall TJ (2010) CXCR7 protein is not expressed on human or mouse leukocytes. J Immunol 185(9):5130–5139

    Article  PubMed  CAS  Google Scholar 

  55. Nagasawa T, Hirota S, Tachibana K, Takakura N, Nishikawa S, Kitamura Y, Yoshida N, Kikutani H, Kishimoto T (1996) Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature 382(6592):635–638

    Article  PubMed  CAS  Google Scholar 

  56. Zou YR, Kottmann AH, Kuroda M, Taniuchi I, Littman DR (1998) Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature 393(6685):595–599

    Article  PubMed  CAS  Google Scholar 

  57. Tachibana K, Hirota S, Iizasa H, Yoshida H, Kawabata K, Kataoka Y, Kitamura Y, Matsushima K, Yoshida N, Nishikawa S, Kishimoto T, Nagasawa T (1998) The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract. Nature 393(6685):591–594

    Article  PubMed  CAS  Google Scholar 

  58. Ma Q, Jones D, Borghesani PR, Segal RA, Nagasawa T, Kishimoto T, Bronson RT, Springer TA (1998) Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice. Proc Natl Acad Sci USA 95(16):9448–9453

    Article  PubMed  CAS  Google Scholar 

  59. 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(4):463–471

    Article  PubMed  CAS  Google Scholar 

  60. Tzeng Y, Li H, Kang Y, Chen W, Cheng W, Lai D (2011) Loss of Cxcl12/Sdf-1 in adult mice decreases the quiescent state of hematopoietic stem/progenitor cells and alters the pattern of hematopoietic regeneration after myelosuppression. Blood 117(2):429–439

    Article  PubMed  CAS  Google Scholar 

  61. Liles WC, Broxmeyer HE, Rodger E, Wood B, Hübel K, Cooper S, Hangoc G, Bridger GJ, Henson GW, Calandra G, Dale DC (2003) Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD3100, a CXCR4 antagonist. Blood 102(8):2728–2730

    Article  PubMed  CAS  Google Scholar 

  62. Broxmeyer HE, Orschell CM, Clapp DW, Hangoc G, Cooper S, Plett PA, Liles WC, Li X, Graham-Evans B, Campbell TB, Calandra G, Bridger G, Dale DC, Srour EF (2005) Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist. J Exp Med 201(8):1307–1318

    Article  PubMed  CAS  Google Scholar 

  63. Hernandez PA, Gorlin RJ, Lukens JN, Taniuchi S, Bohinjec J, Francois F, Klotman ME, Diaz GA (2003) Mutations in the chemokine receptor gene CXCR4 are associated with WHIM syndrome, a combined immunodeficiency disease. Nat Genet 34(1):70–74

    Article  PubMed  CAS  Google Scholar 

  64. Kawai T, Malech HL (2009) WHIM syndrome: congenital immune deficiency disease. Curr Opin Hematol 16(1):20–26

    Article  PubMed  CAS  Google Scholar 

  65. Kawai T, Choi U, Cardwell L, DeRavin SS, Naumann N, Whiting-Theobald NL, Linton GF, Moon J, Murphy PM, Malech HL (2007) WHIM syndrome myelokathexis reproduced in the NOD/SCID mouse xenotransplant model engrafted with healthy human stem cells transduced with C-terminus-truncated CXCR4. Blood 109(1):78–84

    Article  PubMed  CAS  Google Scholar 

  66. Walters KB, Green JM, Surfus JC, Yoo SK, Huttenlocher A (2010) Live imaging of neutrophil motility in a zebrafish model of WHIM syndrome. Blood 116(15):2803–2811

    Article  PubMed  CAS  Google Scholar 

  67. Gulino AV, Moratto D, Sozzani S, Cavadini P, Otero K, Tassone L, Imberti L, Pirovano S, Notarangelo LD, Soresina R, Mazzolari E, Nelson DL, Notarangelo LD, Badolato R (2004) Altered leukocyte response to CXCL12 in patients with warts hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome. Blood 104(2):444–452

    Article  PubMed  CAS  Google Scholar 

  68. Balabanian K, Lagane B, Pablos JL, Laurent L, Planchenault T, Verola O, Lebbe C, Kerob D, Dupuy A, Hermine O, Nicolas J, Latger-Cannard V, Bensoussan D, Bordigoni P, Baleux F, Le Deist F, Virelizier J, Arenzana-Seisdedos F, Bachelerie F (2005) WHIM syndromes with different genetic anomalies are accounted for by impaired CXCR4 desensitization to CXCL12. Blood 105(6):2449–2457

    Article  PubMed  CAS  Google Scholar 

  69. Kawai T, Choi U, Whiting-Theobald NL, Linton GF, Brenner S, Sechler JMG, Murphy PM, Malech HL (2005) Enhanced function with decreased internalization of carboxy-terminus truncated CXCR4 responsible for WHIM syndrome. Exp Hematol 33(4):460–468

    Article  PubMed  CAS  Google Scholar 

  70. Lagane B, Chow KYC, Balabanian K, Levoye A, Harriague J, Planchenault T, Baleux F, Gunera-Saad N, Arenzana-Seisdedos F, Bachelerie F (2008) CXCR4 dimerization and beta-arrestin-mediated signaling account for the enhanced chemotaxis to CXCL12 in WHIM syndrome. Blood 112(1):34–44

    Article  PubMed  CAS  Google Scholar 

  71. McCormick PJ, Segarra M, Gasperini P, Gulino AV, Tosato G (2009) Impaired recruitment of Grk6 and beta-Arrestin 2 causes delayed internalization and desensitization of a WHIM syndrome-associated CXCR4 mutant receptor. PLoS ONE 4(12):e8102

    Article  PubMed  Google Scholar 

  72. Busillo JM, Armando S, Sengupta R, Meucci O, Bouvier M, Benovic JL (2010) Site-specific phosphorylation of CXCR4 is dynamically regulated by multiple kinases and results in differential modulation of CXCR4 signaling. J Biol Chem 285(10):7805–7817

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  74. King AG, Horowitz D, Dillon SB, Levin R, Farese AM, MacVittie TJ, Pelus LM (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(6):1534–1542

    Article  PubMed  CAS  Google Scholar 

  75. Eash KJ, Greenbaum AM, Gopalan PK, Link DC (2010) CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow. J Clin Invest 120(7):2423–2431

    Article  PubMed  CAS  Google Scholar 

  76. Köhler A, De Filippo K, Hasenberg M, van den Brandt C, Nye E, Hosking MP, Lane TE, Männ L, Ransohoff RM, Hauser AE, Winter O, Schraven B, Geiger H, Hogg N, Gunzer M (2011) G-CSF-mediated thrombopoietin release triggers neutrophil motility and mobilization from bone marrow via induction of Cxcr2 ligands. Blood 117(16):4349–4357

    Article  PubMed  Google Scholar 

  77. Wengner AM, Pitchford SC, Furze RC, Rankin SM (2008) The coordinated action of G-CSF and ELR + CXC chemokines in neutrophil mobilization during acute inflammation. Blood 111(1):42–49

    Article  PubMed  CAS  Google Scholar 

  78. Cacalano G, Lee J, Kikly K, Ryan AM, Pitts-Meek S, Hultgren B, Wood WI, Moore MW (1994) Neutrophil and B cell expansion in mice that lack the murine IL-8 receptor homolog. Science 265(5172):682–684

    Article  PubMed  CAS  Google Scholar 

  79. Shuster DE, Kehrli ME, Ackermann MR (1995) Neutrophilia in mice that lack the murine IL-8 receptor homolog. Science 269(5230):1590–1591

    Article  PubMed  CAS  Google Scholar 

  80. Broxmeyer HE, Cooper S, Cacalano G, Hague NL, Bailish E, Moore MW (1996) Involvement of Interleukin (IL) 8 receptor in negative regulation of myeloid progenitor cells in vivo: evidence from mice lacking the murine IL-8 receptor homologue. J Exp Med 184(5):1825–1832

    Article  PubMed  CAS  Google Scholar 

  81. Kawakami M, Tsutsumi H, Kumakawa T, Abe H, Hirai M, Kurosawa S, Mori M, Fukushima M (1990) Levels of serum granulocyte colony-stimulating factor in patients with infections. Blood 76(10):1962–1964

    PubMed  CAS  Google Scholar 

  82. Delano MJ, Kelly-Scumpia KM, Thayer TC, Winfield RD, Scumpia PO, Cuenca AG, Harrington PB, O’Malley KA, Warner E, Gabrilovich S, Mathews CE, Laface D, Heyworth PG, Ramphal R, Strieter RM, Moldawer LL, Efron PA (2011) Neutrophil mobilization from the bone marrow during polymicrobial sepsis is dependent on CXCL12 signaling. J Immunol 187(2):911–918

    Article  PubMed  CAS  Google Scholar 

  83. Richardson RM, Tokunaga K, Marjoram R, Sata T, Snyderman R (2003) Interleukin-8-mediated heterologous receptor internalization provides resistance to HIV-1 infectivity: Role of signal strength and receptor desensitization. J Biol Chem 278(18):15867–15873

    Article  PubMed  CAS  Google Scholar 

  84. Christopher MJ, Rao M, Liu F, Woloszynek JR, Link DC (2011) Expression of the G-CSF receptor in monocytic cells is sufficient to mediate hematopoietic progenitor mobilization by G-CSF in mice. J Exp Med 208(2):251–260

    Article  PubMed  CAS  Google Scholar 

  85. Balabanian K, Levoye A, Klemm L, Lagane B, Hermine O, Harriague J, Baleux F, Arenzana-Seisdedos F, Bachelerie F (2008) Leukocyte analysis from WHIM syndrome patients reveals a pivotal role for GRK3 in CXCR4 signaling. J Clin Invest 118(3):1074–1084

    PubMed  CAS  Google Scholar 

  86. Bradley ME, Bond ME, Manini J, Brown Z, Charlton SJ (2009) SB265610 is an allosteric, inverse agonist at the human CXCR2 receptor. Br J Pharmacol 158(1):328–338

    Article  PubMed  CAS  Google Scholar 

  87. Holz O, Khalilieh S, Ludwig-Sengpiel A, Watz H, Stryszak P, Soni P, Tsai M, Sadeh J, Magnussen H (2010) SCH527123, a novel CXCR2 antagonist, inhibits ozone-induced neutrophilia in healthy subjects. Eur Respir J 35(3):564–570

    Article  PubMed  CAS  Google Scholar 

  88. Lazaar AL, Sweeney LE, Macdonald AJ, Alexis NE, Chen C, Tal-Singer R (2011) SB-656933, a novel CXCR2 selective antagonist, inhibits ex vivo neutrophil activation and ozone-induced airway inflammation in humans. Br J Clin Pharmacol 72(2):282–293

    Article  PubMed  CAS  Google Scholar 

  89. Burger JA, Peled A (2009) CXCR4 antagonists: targeting the microenvironment in leukemia and other cancers. Leukemia 23(1):43–52

    Article  PubMed  CAS  Google Scholar 

  90. Lazennec G, Richmond A (2010) Chemokines and chemokine receptors: new insights into cancer-related inflammation. Trends Mol Med 16(3):133–144

    Article  PubMed  CAS  Google Scholar 

  91. Hendrix CW, Flexner C, MacFarland RT, Giandomenico C, Fuchs EJ, Redpath E, Bridger G, Henson GW (2000) Pharmacokinetics and safety of AMD-3100, a novel antagonist of the CXCR-4 chemokine receptor, in human volunteers. Antimicrob Agents Chemother 44(6):1667–1673

    Article  PubMed  CAS  Google Scholar 

  92. Hendrix CW, Collier AC, Lederman MM, Schols D, Pollard RB, Brown S, Jackson JB, Coombs RW, Glesby MJ, Flexner CW, Bridger GJ, Badel K, MacFarland RT, Henson GW, Calandra G (2004) Safety, pharmacokinetics, and antiviral activity of AMD3100, a selective CXCR4 receptor inhibitor, in HIV-1 infection. J Acquir Immune Defic Syndr 37(2):1253–1262

    Article  PubMed  CAS  Google Scholar 

  93. McCandless EE, Wang Q, Woerner BM, Harper JM, Klein RS (2006) CXCL12 limits inflammation by localizing mononuclear infiltrates to the perivascular space during experimental autoimmune encephalomyelitis. J Immunol 177(11):8053–8064

    PubMed  CAS  Google Scholar 

  94. Matthys P, Hatse S, Vermeire K, Wuyts A, Bridger G, Henson GW, De Clercq E, Billiau A, Schols D (2001) AMD3100, a potent and specific antagonist of the stromal cell-derived factor-1 chemokine receptor CXCR4, inhibits autoimmune joint inflammation in IFN-gamma receptor-deficient mice. J Immunol 167(8):4686–4692

    PubMed  CAS  Google Scholar 

  95. Lukacs NW, Berlin A, Schols D, Skerlj RT, Bridger GJ (2002) AMD3100, a CxCR4 antagonist, attenuates allergic lung inflammation and airway hyperreactivity. Am J Pathol 160(4):1353–1360

    Article  PubMed  CAS  Google Scholar 

  96. Xia X-M, Wang F-Y, Xu W-A, Wang Z-K, Liu J, Lu Y-K, Jin X-X, Lu H, Shen Y-Z (2010) CXCR4 antagonist AMD3100 attenuates colonic damage in mice with experimental colitis. World J Gastroenterol 16(23):2873–2880

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Daniel C. Link.

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Day, R.B., Link, D.C. Regulation of neutrophil trafficking from the bone marrow. Cell. Mol. Life Sci. 69, 1415–1423 (2012). https://doi.org/10.1007/s00018-011-0870-8

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  • DOI: https://doi.org/10.1007/s00018-011-0870-8

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