Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effect of the human ligand for flt-3 (FL) on the committed progenitor colony formation of normal bone marrow (BM) (n = 9) and BM from four aplastic anaemia (AA) and three Diamond-Blackfan anaemia (DBA) patients. Methylcellulose committed progenitor cell assays were carried out using FL alone and in combinations with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3) and c-kit ligand (KL). FL alone had a limited, though significant, effect on the production of granulocyte-macrophage colony-forming unit (CFU-GM) colonies from normal BM and showed an additive effect with IL-3 and GM-CSF separately, but not in combination. FL did not increase the stimulation of KL and did not have an effect on the production of erythroid progenitor colonies. FL had no effect on the AA and DBA BMs studied.
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PMID:The effect of human flt-3 ligand on committed progenitor cell production from normal, aplastic anaemia and Diamond-Blackfan anaemia bone marrow. 855 52

An abnormal bone marrow microenvironment and hematopoietic growth factors are considered as one of the possible mechanisms of aplastic anemia. Circulating levels of erythropoietin, granulocyte colony-stimulating factor (G-GSF), granulocyte-macrophage colony-stimulating factor (GM-GSF) and thrombopoietin are significantly higher in patients with aplastic anemia than in normal controls. Of the two hematopoietic growth factors, acting at the early stages of hematopoiesis, circulating levels of flt-3 ligand are highly elevated in patients with aplastic anemia, whereas those of stem cell factor (SCF) are essentially normal. Decreased production has been described only for interleukin (IL) 1. This may reflect defective monocyte-macrophage maturation in patients with aplastic anemia. Marrow stromal cells are thought to exert a regulatory role in hematopoiesis, at least in part, by the production of certain hematopoietic growth factors. The abilities of stromal cells to produce hematopoietic growth factors, including G-GSF, GM-CSF, IL-6 and SCF, are either normal or elevated in the majority of patients. Thus, the deficiencies of hematopoietic growth factors are unlikely to be the cause of aplastic anemia.
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PMID:Hematopoietic growth factors and marrow stroma in aplastic anemia. 971 65

The hematopoietic sequelae of intramuscular administration of flt-3 ligand (FL) and granulocyte-macrophage colony-stimulating factor (GM-CSF) alone, or in combination, were compared in BALB/c mice. Changes in hematopoiesis were measured in the marrow, spleen and blood using an in vitro colony-forming unit (CFU) assay and flow cytometrically (expression of CD34 and stem cell antigen (Sca)-1). FL administration was associated with a significant increase in the absolute number of CFU and CD34+ cells in the marrow and CFU, CD34+, Sca-1+, and CD34+ Sca-1+ cells in the spleen and blood. These data demonstrate that FL expands and mobilizes a range of hematopoietic progenitors. By comparison, GM-CSF administration was associated with a significant increase in the number of CFU in the spleen and a significant reduction in marrow CD34+, Sca-1+, and CD34+Sca-1+ cells. These data suggest that GM-CSF-driven expansion of CFU may be at the expense of more primitive cells. The pattern of progenitor cell expansion associated with FL + GM-CSF administration was similar to that of FL alone with the following exceptions. The numbers of spleen and blood CFU were significantly greater and the number of marrow CD34+Sca-1+ cells were significantly less, than with FL alone. These data suggest that co-administration of these cytokines may combine the expansion of the more primitive cell populations (associated with FL) with the expansion of the more mature CFU population (associated with GM-CSF) to yield a greater overall CFU expansion and elevation of CFU in the blood. However, increasing the expansion and mobilization of the relatively mature, rather than the more primitive, hematopoietic progenitors, may be of limited value as a mobilization strategy, if the goal is the expansion and isolation of increased numbers of "high-quality," primitive cells for transplantation.
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PMID:Comparison of the hematopoietic activity of flt-3 ligand and granulocyte-macrophage colony-stimulating factor acting alone or in combination. 1109 95

We tried to efficiently generate human dendritic cells (DCs) from CD34+ peripheral blood hematopoietic progenitor cells mobilized by high-dose chemotherapy and subsequent administration of granulocyte colony-stimulating factor, using a liquid suspension culture system. Among various combinations, the combination of c-kit ligand, flt-3 ligand, c-mpl ligand (TPO), and interleukin (IL)-4 most potently generated the number of CD1a+CD14- DCs in cultures containing granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor alpha (TNF-alpha). The delayed addition of IL-4 on day 6 of culture gave rise to an additional increase in the yield of CD1a+CD14-DCs that were characterized by the expression of HLA-ABC, HLA-DR, CD80, CD86, and CD83. The majority of the sorted CD1a-CD14+ cells derived from 6-day culture of CD34+ cells gave rise to CD1a+CD14- DCs and CD1a-CD14+ macrophages on day 12 of culture in the presence and absence of IL-4, respectively. These findings suggest that IL-4 promotes the differentiation of CD1a- CD14+ cells derived from mobilized CD34+ peripheral blood hematopoietic progenitors to CD1a+ CD14- DCs. The majority of these DCs expressed CD68 but not the Langerhans-associated granule antigen, a finding that suggests they emerge through the monocyte differentiation pathway. The addition of TPO and IL-4 to cultures did not affect the potential of DCs to stimulate the primary allogeneic T-cell response. These findings demonstrated that the combination of c-kit ligand plus flt-3 ligand plus TPO with GM-CSF plus TNF-alpha, followed by IL-4, is useful for ex vivo generation of human DCs from mobilized CD34+ peripheral blood progenitors.
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PMID:Efficient ex vivo generation of human dendritic cells from mobilized CD34+ peripheral blood progenitors. 1172 65

Since dendritic cells (DC) play pivotal roles in both innate and adaptive immunity, DC can be a good target for immuno-gene therapy. However, the optimal generation method for gene-modified DC has not yet been well exploited. CD34+ cells from cord blood (CB), bone marrow (BM), or peripheral blood (PB) were expanded in a medium containing stem cell factor (SCF), flt 3 ligand (Flt3L) and thrombopoietin (TPO) with or without HESS-5, a murine BM stromal cell line, for 2 weeks (the first expansion step), then differentiated to DC in a medium containing granulocyte-macrophage colony-stimulating factor (GM-CSF), flt 3 ligand (Flt3L), stem cell factor (SCF), tumor necrosis factor-alpha (TNF-alpha), IL-4, and lipopolysaccharide (LPS) for 9 days (the second differentiation step). DC progenitors were transduced with human immunodeficiency virus (HIV) vectors at different time points during the second step. Use of HESS-5 during the first step resulted in more DC generation than without it (cell expansion: CB, 10,461 vs. 354-fold; BM, 962 vs. 225-fold; peripheral blood mononuclear cell (PBMC), 8,506 vs. 240-fold; %DC: CB, 83.4% vs. 76.9%; BM, 83.6 vs. 69.8%; PBMC, 85.9 vs. 60.5%). Gene transduction to the in vitro expanded DC progenitors at day 3 during the second step, resulted in better final yield of the gene-modified DC than that to those at day 0 or day 6 (as much as 44% of DC expressed green fluorescence protein (GFP) as a transgene) and the transduction efficiency correlated with endocytic ability and percent of S phase. DC transduced with an HIV vector encoding a melanoma antigen, MART-1, were adequately recognized by specific anti-MART-1 CTL. The two-step culture method with HESS-5 is useful for rapid expansion of DC progenitors and subsequent lentiviral gene transduction to DC.
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PMID:Rapid and efficient generation of lentivirally gene-modified dendritic cells from DC progenitors with bone marrow stromal cells. 1244 38

Differentiation of hematopoietic progenitors to dendritic cells (DCs) is a complex, poorly understood process regulated by cytokines, colony-stimulating factors, growth factor receptors, and transcription factors. However, nutritional factors may play an important role. Vitamin A is essential for proper immune function and is implicated in the development of myeloid lineage cells, especially granulocytes. We investigated the role of vitamin A in the differentiation of myeloid DCs. Cultures of bone marrow cells from mice stimulated with granulocyte-macrophage colony-stimulating factor (GM-CSF) in medium with reduced serum retinol demonstrated significantly decreased DC development compared with control cultures containing retinol. Surprisingly, granulocytes predominated in cultures stimulated with GM-CSF when retinol was depleted. The addition of all-trans or 9-cis retinoic acid to cultures depleted of retinol significantly restored DCs and inhibited granulocyte development. The DC-promoting effect of vitamin A was specific to myeloid lineage development stimulated by GM-CSF because vitamin A significantly inhibited DC development stimulated by flt-3 ligand. Vitamin A also affected DC major histocompatibility complex (MHC) class II and costimulatory molecule expression. In response to increasing concentrations of vitamin A, the expression of MHC class II decreased on the DC, whereas the expression of costimulatory molecules increased, especially CD86. Our data suggest that vitamin A favors the differentiation of myeloid progenitors to immature myeloid DC instead of granulocytes when dietary vitamin A is adequate, and that vitamin A deficiency may compromise adaptive immune responses that depend on myeloid DC antigen presentation.
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PMID:Physiological concentrations of retinoic acid favor myeloid dendritic cell development over granulocyte development in cultures of bone marrow cells from mice. 1546 62