Effects of recombinant human granulocyte colony-stimulating factor on hematopoietic progenitor cells in cancer patients

Dührsen, Ulrich; Villeval, Jean‐Luc; Boyd, James H.; Kannourakis, George; Morstyn, George; Metcalf, Donald

doi:10.1182/blood.v72.6.2074.2074

Cited by 552 publications

(106 citation statements)

References 29 publications

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“…This may be due to the entry of new immature neutrophils into the circulation induced by G-CSF administration, since this cytokine is known to stimulate the proliferation and differentiation of progenitor cells committed to the neutrophil lineage [19][20][21][22]. It also increases the absolute number of circulating progenitor cells, including granulocytes, by up to 100-fold after 4 days of treatment, which remains high 2 days after cessation of therapy [23]. In addition, a combination therapy of IL-1b and TNF-a provides a synergistic protective effect against pulmonary P. aeruginosa challenge in granulocytopenic hosts [1,5].…”

Section: Discussionmentioning

confidence: 99%

Protective effect of granulocyte colony-stimulating factor (G-CSF) in a granulocytopenic mouse model of Pseudomonas aeruginosa lung infection through enhanced phagocytosis and killing by alveolar macrophages through priming tumour necrosis factor-alpha (TNF-α) production

Shirai

Kadota

Tomono

et al. 1997

Clinical and Experimental Immunology

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SUMMARYWe investigated the effects of G-CSF in a granulocytopenic mouse model of Pseudomonas aeruginosa lung infection. The model was prepared by intratracheal instillation of the bacteria, while granulocytopenia was induced by intraperitoneal injection of 4 . 0 mg of cyclophosphamide (CPA). There was no difference in the survival rate between G-CSF-treated animals and the normal group, and the number of neutrophils in the blood and lung recovered to normal in the former group. However, the phagocytic and killing activities of neutrophils were lower in G-CSF-treated mice than in controls. Interestingly, the mortality rate increased significantly when anti-TNF-a antibody was combined with G-CSF, although it was intermediate between CPA alone and CPA-G-CSF-treated mice. However, the improved mortality was not associated with a change in the number of neutrophils in the circulation and lung. Administration of anti-TNF-a antibody resulted in a significant suppression of TNF-a in bronchoalveolar lavage fluid and of enhanced alveolar macrophage function (phagocytic and bactericidal activity) against P. aeruginosa in G-CSF-treated granulocytopenic mice. We showed also increased TNF-a mRNA expression and TNF-a production in vitro using G-CSF-pretreated alveolar macrophages compared with control untreated macrophages. Our results are the first evidence to suggest that G-CSF provides a synergistic protective effect against lethal P. aeruginosa lung infection in the granulocytopenic host. This effect is probably due to enhancement of alveolar macrophage function through endogenous TNF-a production, in addition to increasing the number of circulating neutrophils.

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Section: Discussionmentioning

confidence: 99%

Protective effect of granulocyte colony-stimulating factor (G-CSF) in a granulocytopenic mouse model of Pseudomonas aeruginosa lung infection through enhanced phagocytosis and killing by alveolar macrophages through priming tumour necrosis factor-alpha (TNF-α) production

Shirai

Kadota

Tomono

et al. 1997

Clinical and Experimental Immunology

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“…Haemopoietic cytokines such as granulocyte colony-stimulating factor (G-CSF) have the remarkable ability to induce large numbers of haemopoietic progenitor cells to circulate in the blood (Duhrsen et al, 1988;Gordon, 1993;Bodine, 1995). The phenomenon of induced progenitor cell circulation has been widely exploited as a means of harvesting haemopoietic cells for transplantation (Kessinger & Armitage, 1991;Gale et al, 1992;Pettengell et al, 1992).…”

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confidence: 99%

Biological properties of peripheral blood progenitor cells mobilized by cyclophosphamide and granulocyte colony‐stimulating factor

et al. 1997

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Patients transplanted with mobilized blood progenitor cells (PBPC) recover their neutrophil counts more rapidly than patients transplanted with bone marrow even when they receive the same dose/kg of granulocyte‐macrophage colony‐forming cells (CFU‐GM). Here we have sought a biological explanation for this phenomenon. Most CD34‐positive PBPC are quiescent (<1% in S phase) when they are collected from the bloodstream of patients treated with cyclophosphamide and granulocyte colony‐stimulating factor (G‐CSF), but we have shown that they are able to resume proliferation rapidly in vitro by measuring the kinetics of CFU‐GM production by primitive plastic‐adherent (PΔ) cells. Also, PΔcells in PBPC harvests, unlike normal marrow PΔ cells, were insensitive to cell‐cycle restraint imposed by contact with marrow‐derived stromal cells. We found that PΔ cells in PBPC collections produce relatively more CFU‐GM and relatively fewer BFU‐E than PΔ cells in bone marrow, indicating that granulopoiesis might occur at the expense of erythropoiesis, but we were unable to find any differences in the kinetics of granulocytic maturation between PBPC and bone marrow. Our interpretation of these findings is that transplanted PBPC rapidly enter the cell cycle and contact with stromal cells in the marrow does not reduce the proportion of progenitors participating in neutrophil production. Consequently, neutrophil recovery after PBPC infusion is more rapid than neutrophil recovery after marrow infusion. Granulopoiesis at the expense of erythropoiesis may also contribute to this effect.

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“…Given the expression of the c-mpl on a number CD34 + cells, the observations of progenitor cell mobilization in preclinical models [71], and the unexpected observations during phase 1 studies of G-CSF [72], we assessed the levels of PBPC, when given alone and when used in combination with filgrastim after chemotherapy.…”

Section: Peripheral Blood Progenitor Cell (Pbpc) Mobilizationmentioning

confidence: 99%

Megakaryocyte Growth and Development Factor: A Review of Early Clinical Studies

Abraham

Basser

1997

The Oncologist

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Megakaryocyte growth and development factor (MGDF), a Mpl ligand, recently entered clinical trials worldwide and has been demonstrated to have potent biological activity. MGDF administration causes a dose‐dependent increase in platelet count but no effect on white cell count or hematocrit. These platelets are morphologically and functionally normal. When administered following moderately myelosuppressive chemotherapy, MGDF significantly enhances platelet recovery, although scheduling in relation to chemotherapy may be important in optimizing the full effects. MGDF mobilizes progenitor cells of multiple hematopoietic lineages, and may enhance the effects of filgrastim on peripheral blood progenitor cell levels after chemotherapy. MGDF is well tolerated and does not cause toxicity similar to that observed with other thrombopoietic cytokines. Numerous studies are under way to help determine the precise role of MGDF in clinical practice.

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Effects of recombinant human granulocyte colony-stimulating factor on hematopoietic progenitor cells in cancer patients

Cited by 552 publications

References 29 publications

Protective effect of granulocyte colony-stimulating factor (G-CSF) in a granulocytopenic mouse model of Pseudomonas aeruginosa lung infection through enhanced phagocytosis and killing by alveolar macrophages through priming tumour necrosis factor-alpha (TNF-α) production

Protective effect of granulocyte colony-stimulating factor (G-CSF) in a granulocytopenic mouse model of Pseudomonas aeruginosa lung infection through enhanced phagocytosis and killing by alveolar macrophages through priming tumour necrosis factor-alpha (TNF-α) production

Biological properties of peripheral blood progenitor cells mobilized by cyclophosphamide and granulocyte colony‐stimulating factor

Megakaryocyte Growth and Development Factor: A Review of Early Clinical Studies

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