PMID- 12595315
OWN - NLM
STAT- MEDLINE
DCOM- 20040204
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 101
IP  - 12
DP  - 2003 Jun 15
TI  - The role of G-protein signaling in hematopoietic stem/progenitor cell 
      mobilization.
PG  - 4739-47
AB  - 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, beta2 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.
FAU - Papayannopoulou, Thalia
AU  - Papayannopoulou T
AD  - Division of Hematology, University of Washington, Seattle 98195, USA. 
      thalp@u.washington.edu
FAU - Priestley, Gregory V
AU  - Priestley GV
FAU - Bonig, Halvard
AU  - Bonig H
FAU - Nakamoto, Betty
AU  - Nakamoto B
LA  - eng
GR  - HL46557/HL/NHLBI NIH HHS/United States
GR  - HL58734/HL/NHLBI NIH HHS/United States
GR  - RR00166/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030220
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antibodies)
RN  - 0 (CD18 Antigens)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Integrin alpha4beta1)
RN  - 0 (Polysaccharides)
RN  - 0 (Receptors, Granulocyte Colony-Stimulating Factor)
RN  - 0 (Selectins)
RN  - 143011-72-7 (Granulocyte Colony-Stimulating Factor)
RN  - 143198-26-9 (Integrin alpha4)
RN  - 9072-19-9 (fucoidan)
RN  - EC 2.4.2.31 (Pertussis Toxin)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
MH  - Animals
MH  - Antibodies/pharmacology
MH  - Bone Marrow Cells/cytology/immunology
MH  - CD18 Antigens/physiology
MH  - Cell Movement
MH  - Chemokine CCL2/deficiency
MH  - Colony-Forming Units Assay
MH  - Drug Synergism
MH  - GTP-Binding Proteins/*physiology
MH  - Granulocyte Colony-Stimulating Factor/pharmacology
MH  - *Hematopoietic Stem Cell Mobilization
MH  - Hematopoietic Stem Cells/*cytology/immunology
MH  - Immunophenotyping
MH  - Integrin alpha4/immunology
MH  - Integrin alpha4beta1/antagonists & inhibitors
MH  - Kinetics
MH  - Leukocytosis
MH  - Matrix Metalloproteinase 9/deficiency/physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Pertussis Toxin/pharmacology
MH  - Polysaccharides/pharmacology
MH  - Receptors, Granulocyte Colony-Stimulating Factor/deficiency
MH  - Selectins/physiology
MH  - *Signal Transduction
MH  - Spleen/cytology
MH  - Stem Cells/*cytology/immunology
EDAT- 2003/02/22 04:00
MHDA- 2004/02/05 05:00
CRDT- 2003/02/22 04:00
PHST- 2003/02/22 04:00 [pubmed]
PHST- 2004/02/05 05:00 [medline]
PHST- 2003/02/22 04:00 [entrez]
AID - S0006-4971(20)50634-4 [pii]
AID - 10.1182/blood-2002-09-2741 [doi]
PST - ppublish
SO  - Blood. 2003 Jun 15;101(12):4739-47. doi: 10.1182/blood-2002-09-2741. Epub 2003 
      Feb 20.