Marrow engraftment of hematopoietic stem and progenitor cells is independent of Gαi-coupled chemokine receptors

Wiesmann, Anne; Spangrude, Gerald J.

doi:10.1016/s0301-472x(99)00029-6

Cited by 42 publications

(43 citation statements)

References 60 publications

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“…Ptx-mobilized cells were more severely crippled in their SDF-1 response than the G-CSF-mobilized cells, although conflicting data are available for the response of G-CSF-mobilized cells to SDF-1. 33,59,60 Moreover, such an exacerbated effect on abrogation of SDF-1 signaling together with a possible reduction of SDF-1 within BM (Table 2) and/or an increase in MMP-9 on day 3 after Ptx treatment could explain the synergy of Ptx with G-CSF that we observed. Nevertheless, the picture is far from clear, and other contradictory interpretations have also surfaced.…”

Section: Discussionmentioning

confidence: 74%

“…[24][25][26] Whether in vivo treatments with polyclonal antibodies versus different CXCR4 antagonistic molecules with potentially different modes of action could account for these differences is difficult to discern at this point and further experimentation is warranted. On a relevant vein, data with in vitro anti-CXCR4 antibody treatments are inconsistent [61][62][63][64] and at odds with studies using Ptx-treated cells in homing experiments of murine BM, 60 murine fetal liver cells, 65 or human CD34 ϩ cells. 62 Collectively, the weight of the evidence suggests that CXCR4/SDF-1 signaling may not be crucial for the initial anchoring of transplanted cells to endothelial cells within BM, but their subsequent retention within BM is greatly dependent on CXCR4/SDF-1 signaling.…”

Section: Discussionmentioning

confidence: 99%

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The role of G-protein signaling in hematopoietic stem/progenitor cell mobilization

Papayannopoulou

Priestley

Bönig

et al. 2003

Blood

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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 G i -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 colonyforming unit-culture (CFU-C) and colonyforming 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

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Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

The role of G-protein signaling in hematopoietic stem/progenitor cell mobilization

Papayannopoulou

Priestley

Bönig

et al. 2003

Blood

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“…9 Purified pertussis toxin (PT) was provided by Dr W. Cieplak (RIBI Immunochem, Hamilton, MT). PT was purified from culture filtrates of Bordetella pertussis strain 3779 BI2S4 by affinity chromatography as previously described.…”

Section: Pertussis Toxin Treatmentmentioning

confidence: 99%

“…To determine the origin of these megakaryocytes, we blocked splenic engraftment of Rho low stem cells by using pertussis toxin. 9 Pertussis toxin irreversibly blocks G␣ i protein-coupled chemokine receptors and has been shown to markedly block splenic engraftment of Rho low stem cells without affecting bone marrow engraftment. Pertussis toxin did not affect the number of megakaryocytes appearing in the spleen, supporting the hypothesis that these megakaryocytes were derived from progenitors arising in the bone marrow.…”

Section: Introductionmentioning

confidence: 99%

The spleen is a major site of megakaryopoiesis following transplantation of murine hematopoietic stem cells

Slayton

Georgelas

Pierce

et al. 2002

Blood

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The stem cell pool can be fractionated by using the mitochondrial dye, rhodamine-123, into Rho low hematopoietic stem cells and Rho high progenitors. Rho low stem cells permanently engraft all lineages, whereas Rho high progenitors transiently produce erythrocytes, without substantial platelet or granulocyte production. We hypothesized that the inability of the Rho high cells to produce platelets in vivo was due to the fact that these cells preferentially engraft in the spleen and lack marrow engraftment. Initially, we demonstrated that Rho high progenitors produced more megakaryocytes in vitro than Rho low stem cells did. To study the activity of the Rho low and Rho high subsets in vivo, we used mice allelic at the hemoglobin and glucose phosphate isomerase loci to track donor-derived erythropoiesis and thrombopoiesis. Rho low stem cells contributed to robust and long-term erythroid and platelet engraftment, whereas Rho high progenitors contributed only to transient erythroid engraftment and produced very low numbers of platelets in vivo. Donorderived megakaryopoiesis occurred at higher densities in the spleen than in the bone marrow in animals receiving Rho low stem cells and peaked around day 28. Blockade of splenic engraftment using pertussis toxin did not affect the peak of splenic megakaryopoiesis, supporting the hypothesis that these megakaryocytes were derived from progenitors that originated in the bone marrow. These data emphasize that in vitro behavior of hematopoietic progenitor cell subsets does not always predict their behavior following transplantation. This study supports a major role for the spleen in thrombopoi IntroductionMurine hematopoietic stem cells have been shown to reside within a population of cells that do not express lineage-specific markers (Lin neg ) and express the antigens Sca-1, c-kit, and Thy-1.1. Cells of this phenotype comprise the stem cell pool in certain strains of mice. 1,2 Rhodamine-123 (Rho) is a mitochondrial dye that stains cells based on their state of activation in which the more metabolically active cells tend to fluoresce brightly and quiescent cells dimly. 3 Rho has been used to subfractionate the stem cell pool into quiescent and metabolically active subsets. The Rho low subset is highly enriched for hematopoietic stem cells, to the degree that as few as 4 of these cells can reconstitute a mouse for the lifetime of the animal. Observations of the behavior of these stem cells have led to the model of the 2-tiered stem-cell pool. 4 According to this model, the Rho low cells make rare contributions to the peripheral compartment, but are mobilized in response to physiologic needs, and represent most of the transplantable stem cells. In contrast, Rho high cells have a high rate of cell division and, thus, make frequent contributions to the peripheral compartment under normal conditions. However, Rho high cells perform poorly in transplantation experiments, producing mainly erythrocytes and contributing little to platelet or granulocyte recovery. 5,6 All previous stu...

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“…58 The finding of a disconnect between in vitro migration to SDF1a and homing and engraftment of GROb-mobilized HSPC is contrary to the hypothesis that the SDF-1/CXCR4 axis is the primary axis involved in HSPC trafficking, engraftment and mobilization. 61,[85][86][87] Additional reports that WBC recovery is faster in patients transplanted with G-CSF-mobilized PBSC than bone marrow cells, 88,89 that G-CSF-mobilized CD34 þ cells migrate less well to SDF-1a in vitro than marrow CD34 þ cells, 70,90 that inhibition of Gai-coupled receptors, which includes CXCR4, by Pertusis toxin does not impair hematopoietic engraftment, 91 that fetal liver cells from CXCR4 À/À mice home and engraft in lethally irradiated recipients, 92 and that marrow engraftment of CXCR4 À/À and CXCR4 þ / þ SKL cells is equivalent 93 also suggest that the SDF-1a/CXCR4 axis may not be absolutely required for engraftment and homing by all HSC populations. Moreover, homing of HPC refractory to SDF-1 migration is blocked in the absence of a4-integrins, indicating that homing via SDF-1a/CXCR4 can be fully compensated by a functional a4-integrin/VCAM-1 pathway.…”

Section: Chemokine Mobilized Hsc Are Differentmentioning

confidence: 99%

Chemokine-mobilized adult stem cells; defining a better hematopoietic graft

Pelus

Fukuda

2007

Leukemia

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Marrow engraftment of hematopoietic stem and progenitor cells is independent of Gαi-coupled chemokine receptors

Cited by 42 publications

References 60 publications

The role of G-protein signaling in hematopoietic stem/progenitor cell mobilization

The role of G-protein signaling in hematopoietic stem/progenitor cell mobilization

The spleen is a major site of megakaryopoiesis following transplantation of murine hematopoietic stem cells

Chemokine-mobilized adult stem cells; defining a better hematopoietic graft

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