|
|
Prepublished online as a Blood First Edition Paper on February 20, 2003; DOI 10.1182/blood-2002-09-2741.
 Previous Article | Table of Contents | Next Article 
Blood, 15 June 2003, Vol. 101, No. 12, pp. 4739-4747
HEMATOPOIESIS
The role of G-protein signaling in hematopoietic stem/progenitor cell mobilization
Thalia Papayannopoulou,
Gregory V. Priestley,
Halvard Bonig, and
Betty Nakamoto
From the Division of Hematology, University of Washington, Seattle.
The directed migration of mature leukocytes to inflammatory sites and the lymphocyte trafficking in vivo are dependent on G protein–coupled receptors and delivered through pertussis toxin (Ptx)–sensitive Gi-protein signaling. In the present study, we explored the in vivo role of G-protein signaling on the redistribution or mobilization of hematopoietic stem/progenitor cells (HPCs). A single injection of Ptx in mice elicits a long-lasting leukocytosis and a progressive increase in circulating colony-forming unit-culture (CFU-C) and colony-forming unit spleen (CFU-S). We found that the prolonged effect is sustained by a continuous slow release of Ptx bound to red blood cells or other cells and is potentially enhanced by an indirect influence on cell proliferation. Plasma levels of certain cytokines (interleukin 6 [IL-6], granulocyte colony-stimulating factor [G-CSF]) increase days after Ptx treatment, but these are unlikely initiators of mobilization. In addition to normal mice, mice genetically deficient in monocyte chemotactic protein 1 (MCP-1), matrix metalloproteinase 9 (MMP-9), G-CSF receptor,  2 integrins, or selectins responded to Ptx treatment, suggesting independence of Ptx-response from the expression of these molecules. Combined treatments of Ptx with anti–very late activation antigen (anti-VLA-4), uncovered potentially important insight in the interplay of chemokines/integrins, and the synergy of Ptx with G-CSF appeared to be dependent on MMP-9. As Ptx-mobilized kit+ cells display virtually no response to stromal-derived factor 1 (SDF-1) in vitro, our data suggest that disruption of CXCR4/SDF-1 signaling may be the underlying mechanism of Ptx-induced mobilization and indirectly reinforce the notion that active signaling through this pathway is required for continuous retention of cells within the bone marrow. Collectively, our data unveil a novel example of mobilization through pharmacologic modulation of signaling.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
T. Papayannopoulou and D. T. Scadden
Stem-cell ecology and stem cells in motion
Blood,
April 15, 2008;
111(8):
3923 - 3930.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. C. Rafii, B. Psaila, J. Butler, D. K. Jin, and D. Lyden
Regulation of Vasculogenesis by Platelet-Mediated Recruitment of Bone Marrow-Derived Cells
Arterioscler. Thromb. Vasc. Biol.,
February 1, 2008;
28(2):
217 - 222.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Zhang, J.-M. Navenot, N. M. Frilot, N. Fujii, and S. C. Peiper
Association of Nucleophosmin Negatively Regulates CXCR4-Mediated G Protein Activation and Chemotaxis
Mol. Pharmacol.,
November 1, 2007;
72(5):
1310 - 1321.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Zhu, O. Boachie-Adjei, B. A. Rawlins, B. Frenkel, A. L. Boskey, L. B. Ivashkiv, and C. P. Blobel
A Novel Regulatory Role for Stromal-derived Factor-1 Signaling in Bone Morphogenic Protein-2 Osteogenic Differentiation of Mesenchymal C2C12 Cells
J. Biol. Chem.,
June 29, 2007;
282(26):
18676 - 18685.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Rossi, R. Manfredini, F. Bertolini, D. Ferrari, M. Fogli, R. Zini, S. Salati, V. Salvestrini, S. Gulinelli, E. Adinolfi, et al.
The extracellular nucleotide UTP is a potent inducer of hematopoietic stem cell migration
Blood,
January 15, 2007;
109(2):
533 - 542.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Iwata, M. Pillai, A. Ramakrishnan, R. C. Hackman, H. J. Deeg, G. Opdenakker, and B. Torok-Storb
Reduced expression of inducible gelatinase B/matrix metalloproteinase-9 in monocytes from patients with myelodysplastic syndrome: correlation of inducible levels with the percentage of cytogenetically marked cells and with marrow cellularity
Blood,
January 1, 2007;
109(1):
85 - 92.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Foudi, P. Jarrier, Y. Zhang, M. Wittner, J.-F. Geay, Y. Lecluse, T. Nagasawa, W. Vainchenker, and F. Louache
Reduced retention of radioprotective hematopoietic cells within the bone marrow microenvironment in CXCR4-/- chimeric mice
Blood,
March 15, 2006;
107(6):
2243 - 2251.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Burroughs, M. Mielcarek, M.-T. Little, G. Bridger, R. MacFarland, S. Fricker, J. Labrecque, B. M. Sandmaier, and R. Storb
Durable engraftment of AMD3100-mobilized autologous and allogeneic peripheral-blood mononuclear cells in a canine transplantation model
Blood,
December 1, 2005;
106(12):
4002 - 4008.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Bonig, G. V. Priestley, L. M. Nilsson, Y. Jiang, and T. Papayannopoulou
PTX-sensitive signals in bone marrow homing of fetal and adult hematopoietic progenitor cells
Blood,
October 15, 2004;
104(8):
2299 - 2306.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. V. Gulino, D. Moratto, S. Sozzani, P. Cavadini, K. Otero, L. Tassone, L. Imberti, S. Pirovano, L. D. Notarangelo, R. Soresina, et al.
Altered leukocyte response to CXCL12 in patients with warts hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome
Blood,
July 15, 2004;
104(2):
444 - 452.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Badolato
Leukocyte circulation: one-way or round-trip? Lessons from primary immunodeficiency patients
J. Leukoc. Biol.,
July 1, 2004;
76(1):
1 - 6.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-P. Levesque, F. Liu, P. J. Simmons, T. Betsuyaku, R. M. Senior, C. Pham, and D. C. Link
Characterization of hematopoietic progenitor mobilization in protease-deficient mice
Blood,
July 1, 2004;
104(1):
65 - 72.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Spiegel, O. Kollet, A. Peled, L. Abel, A. Nagler, B. Bielorai, G. Rechavi, J. Vormoor, and T. Lapidot
Unique SDF-1-induced activation of human precursor-B ALL cells as a result of altered CXCR4 expression and signaling
Blood,
April 15, 2004;
103(8):
2900 - 2907.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Devine, N. Flomenberg, D. H. Vesole, J. Liesveld, D. Weisdorf, K. Badel, G. Calandra, and J. F. DiPersio
Rapid Mobilization of CD34+ Cells Following Administration of the CXCR4 Antagonist AMD3100 to Patients With Multiple Myeloma and Non-Hodgkin's Lymphoma
J. Clin. Oncol.,
March 15, 2004;
22(6):
1095 - 1102.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Ratajczak, R. Reca, M. Kucia, M. Majka, D. J. Allendorf, J. T. Baran, A. Janowska-Wieczorek, R. A. Wetsel, G. D. Ross, and M. Z. Ratajczak
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,
March 15, 2004;
103(6):
2071 - 2078.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Papayannopoulou
Current mechanistic scenarios in hematopoietic stem/progenitor cell mobilization
Blood,
March 1, 2004;
103(5):
1580 - 1585.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. M. Pelus, H. Bian, A. G. King, and S. Fukuda
Neutrophil-derived MMP-9 mediates synergistic mobilization of hematopoietic stem and progenitor cells by the combination of G-CSF and the chemokines GRO{beta}/CXCL2 and GRO{beta}T /CXCL2{Delta}4
Blood,
January 1, 2004;
103(1):
110 - 119.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. H. Cottler-Fox, T. Lapidot, I. Petit, O. Kollet, J. F. DiPersio, D. Link, and S. Devine
Stem Cell Mobilization
Hematology,
January 1, 2003;
2003(1):
419 - 437.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
