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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)

Erythropoietin or colony-stimulating factor, or both, were added to rat or mouse marrow cell cultures, and the responses to each inducer were measured. Colony-stimulating factor caused the suppression of erythropoietin-stimulated hemoglobin synthesis, and erythropoietin caused the suppression of the granulocyte-macrophage colony formation that is dependent on colony-stimulating factor. The extent of suppression by each inducer was dose-dependent. Marrow cells from plethoric rats were more sensitive to suppression of erythropoietin action by colony-stimulating factor than were normal marrow cells. These findings suggest that either (i) the receptors for erythropoietin and for colony-stimulating factor have overlapping specificities and that the "wrong" inducer may bind without having an inductive effect, or (ii) the target cells for erythropoietin and colony-stimulating factor are very closely related or are the same.
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PMID:Simultaneous effects of erythropoietin and colony-stimulating factor on bone marrow cells. 30 86

Differentiation and proliferation of almost all hemopoietic cell lines can now be studied in vitro. Cloning techniques and suspension cultures allow the study of proliferation of the multipotential hemopoietic progenitor cell and the committed progenitors for granulocytes, macrophages, eosinophils, megakaryocytes, and erythrocytes. The proliferation of each of the committed progenitor cells is controlled by specific glycoproteins and two of these have recently been purified: granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin. The rate of proliferation of the GM-progenitor cells and their pattern of differentiation depends on the concentration of the hormone. At low concentrations of GM-CSF (10(-11) M) fewer progenitor cells are stimulated and macrophage colonies rather than granulocyte colonies develop. The change in the direction of granulocyte-macrophage differentiation appears to be related to a) the concentration of GM- CSF and b) the different sensitivity of a subpopulation of monocyte colony-forming cells which are responsive to GM-CSF even at low concentrations of the regulator. Analysis of the rate of RNA synthesis by bone marrow cells has shown that GM-CSF stimulates the mature nondividing end cells of differentiation (ie, polymorphs) as well as the progenitor cells. Although GM-CSF and erythropoietin have been radiolabeled, binding studies have been hampered by the loss of biologic activity during the labeling procedure and the heterogeneity of the target cells to which the regulators bind. Surface proteins and receptors for erythrocytes have been well characterized but the relationships between these proteins and the cell surface proteins of nucleated blood cells is not well understood. It appears that some proteins are lost from the cell surface during the development of granulocytes, which are retained on the surface of the B lymphocyte. Other proteins such as chemotactic receptors and complement receptors only appear on the mature cells. External radiolabeling of the granulocyte surface using iodogen yielded a simple profile of 125I-labeled proteins when analyzed by sodium dodecyl sulphate polyacrylamide gel electrophoresis.
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PMID:Regulation of hemopoietic cell differentiation and proliferation. 30 73

Proliferating populations of neutrophils, monocytes, eosinophils, erythroid cells, and T-lymphocytes from normal subjects or patients with various diseases can now be analysed by colony formation in semisolid cultures. These cultures accurately determine the number and proliferative activity of the precursor cells of each population and can also be used to monitor the levels of specific regulatory factors (for example, erythropoietin, colony-stimulating factor) in the serum or urine of such patients. Studies using semisolid cultures have shown that the leukemic cells in chronic and acute myeloid leukemia remain dependent on the normal regulator, granulocyte-macrophage colony-stimulating factor, for proliferation. The cultures have proved valuable in the prognostic assessment of acute leukemic patients and in monitoring impending changes in the clinical status of patients with acute or chronic myeloid leukemia or myeloproliferative disorders.
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PMID:In-vitro cloning techniques for hemopoietic cells: clinical applications. 33 9

Hematopoietic growth factors may mitigate the cytopenias that frequently complicate HIV disease or its treatment. Clinical and in vitro studies have indicated the ability of granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF) or erythropoietin (EPO) to overcome the myelosuppression of HIV or many of the drug therapies used in the care of HIV-infected individuals. In addition, neutrophil or monocyte functional abnormalities observed in AIDS patients may be improved by the use of GM-CSF. Issues which may distinguish the use of hematopoietic growth factors in AIDS as compared with in other clinical settings include: 1) interaction of the growth factor with other cytokines which are aberrantly expressed, 2) direct effects of the growth factor on the replicative activity of HIV, and 3) potential interactions of the growth factor with other concurrently administered medications. This review focuses on the potential roles and limitations of growth factor use in AIDS and reviews the clinical studies using GM-CSF in HIV-infected individuals.
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PMID:The use of GM-CSF in AIDS. 128 4

Receptors for the hematopoietic growth factors erythropoietin, interleukin 3 (IL-3), and granulocyte-macrophage colony-stimulating factor (GM-CSF) are members of a structurally related receptor superfamily. Interestingly, while none of these receptors encode tyrosine kinase activities, induced tyrosine phosphorylation has been observed in various responsive cells stimulated with each factor. Toward defining possible common transduction pathways which are activated by these three cytokines, we have studied induced protein phosphorylation in murine myeloid FDC-P1 cells stably transfected with an erythropoietin receptor cDNA (FDC-ER cells). FDC-ER cells proliferate in response to erythropoietin (Quelle, D. E., and Wojchowski, D. M. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 4801-4805), and presently are shown to rapidly phosphorylate a M(r) 100,000 cytosolic protein (pp100) at tyrosine residues in response to this factor. Phosphorylation of pp100 also is induced in FDC-P1 and FDC-ER cells in response to IL-3 or GM-CSF. Importantly, quantitative analyses showed identical concentration dependencies for factor-induced pp100 phosphorylation and induced cell proliferation. Moreover, a selective loss of proliferative responsiveness to GM-CSF in FDC-ER cells was associated with a reduced capacity of GM-CSF to induce pp100 phosphorylation. Finally, limited differences in tryptic phosphopeptide maps of pp100 as isolated following exposure to erythropoietin, IL-3, or GM-CSF were observed, suggesting that these factors also may preferentially induce phosphorylation of pp100 at distinct sites. These findings are consistent with a role for pp100 as a common cytosolic transducer in the apparently convergent pathways of erythropoietin-, IL-3-, and GM-CSF-induced proliferation of myeloid progenitor cells.
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PMID:Interleukin 3, granulocyte-macrophage colony-stimulating factor, and transfected erythropoietin receptors mediate tyrosine phosphorylation of a common cytosolic protein (pp100) in FDC-ER cells. 132 20

Severe combined immunodeficient (SCID) mice transplanted with human bone marrow were treated with human mast cell growth factor, a fusion of interleukin-3 and granulocyte-macrophage colony-stimulating factor (PIXY321), or both, starting immediately or 1 month later. Immature human cells repopulated the mouse bone marrow with differentiated human cells of multiple myeloid and lymphoid lineages; inclusion of erythropoietin resulted in human red cells in the peripheral blood. The bone marrow of growth factor-treated mice contained both multipotential and committed myeloid and erythroid progenitors, whereas mice not given growth factors had few human cells and only granulocyte-macrophage progenitors. Thus, this system allows the detection of immature human cells, identification of the growth factors that regulate them, and the establishment of animal models of human hematopoietic diseases.
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PMID:Cytokine stimulation of multilineage hematopoiesis from immature human cells engrafted in SCID mice. 137 31

Clinical trials with hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor [GM-CSF], granulocyte colony-stimulating factor [G-CSF], interleukin-3, erythropoietin] have been done in patients with myelodysplastic syndromes. Treatment with GM-CSF or G-CSF has resulted in an increase of neutrophil counts into the normal range in the vast majority of patients. Progression to acute leukemia does not appear to occur more frequently in the patients receiving GM-CSF or G-CSF. Increases in platelet counts and hemoglobin levels have been reported after treatment with interleukin-3 and erythropoietin, respectively, although the response is only seen in a minority of treated patients. Combination therapy with GM-CSF and low-dose cytosine arabinoside has been studied, but present data do not indicate an advantage over other treatment strategies. Cytogenetic and molecular genetic analyses demonstrate that both normal and malignant precursor cells are stimulated by cytokine therapy.
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PMID:Treatment of myelodysplastic syndromes with cytokines and cytotoxic drugs. 137 66

The cDNA encoding human interleukin (IL)-9 has recently been cloned and the recombinant molecule found to enhance erythroid colony formation in vitro by bone marrow, peripheral blood, and cord blood cells. In our present report, recombinant human (rhu) IL-9 was evaluated, alone and in combination with other cytokines, for its effect on colony formation by erythroid progenitor (erythroid burst-forming units, BFU-E) and precursor (erythroid colony-forming units, CFU-E) cells in low density (LD), nonadherent LD density T-lymphocyte-depleted (NALT-), and immunofluorescence-sorted CD34+++DR+ and CD34+++DR+CD33- cells from normal human bone marrow. When highly enriched CD34+++DR+ and CD34+++DR+CD33- cells were plated at 200 and 100 cells/ml in the presence of 5% (vol/vol) 5637-cell-conditioned medium and erythropoietin (Epo) under serum-containing conditions, 46 and 51 day-14 BFU-E were observed, respectively. The enhancing effect of rhuIL-9 was similar to that of 5637 CM on colony formation by Epo-dependent BFU-E and CFU-E in these enriched sorted CD34+++DR+ and CD34+++DR+CD33- cells under serum-containing and serum-depleted culture conditions. No significant synergistic or additive effect of rhuIL-9 was noted when used in conjunction with rhu interleukin 3 (rhuIL-3), rhu interleukin 6 (rhuIL-6), and/or rhu granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) under the same culture conditions. The cloning enhancing effect elicited by human IL-9 is Epo dependent, although IL-9 alone sustains the survival of erythroid progenitor cells in vitro, as assessed by delayed additions of Epo to the cultures. The ability of human IL-9 to stimulate BFU-E and CFU-E colony formation using low numbers of highly enriched progenitor cells in serum-depleted conditions demonstrates the direct effect of IL-9 on erythroid progenitors and implicates its potential role in the enhancement of erythropoiesis.
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PMID:Human interleukin (IL)-9 specifically stimulates proliferation of CD34+++DR+CD33- erythroid progenitors in normal human bone marrow in the absence of serum. 137 87

Using the human erythropoietin-responsive hematopoietic cell line UT-7, we showed that erythropoietin (Epo) rapidly and specifically induced the tyrosine phosphorylation of its own receptor (M(r) 75,000) and increased the tyrosine phosphorylation of other proteins of M(r) 140,000, 120,000, 95,000, 60,000, 57,000, and 42,000. Neither granulocyte-macrophage colony-stimulating factor, interleukin 3, interleukin 6, nor the kit ligand induced the phosphorylation of the M(r) 75,000 receptor protein, although these growth factors induced the phosphorylation of other proteins. Cross-linking experiments using 125I-Epo indicated that the UT-7 cells expressed three Epo receptor subunits, of M(r) 100,000, 85,000, and 75,000, among which only the M(r) 75,000 subunit was tyrosine-phosphorylated following activation with Epo.
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PMID:Erythropoietin induces the tyrosine phosphorylation of its own receptor in human erythropoietin-responsive cells. 137 26

Aplastic anemia (AA) is a rare human bone marrow disorder of unknown etiology manifested by a strongly impaired growth of hematopoietic precursors. In this study, we examined the ability of recombinant human stem cell factor (SCF) to stimulate proliferation in vitro of bone marrow cells from 15 AA patients. All patients had been previously treated with antilymphocyte globulin (ALG). SCF, in combination with erythropoietin (Epo), interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and granulocyte colony-stimulating factor (G-CSF), increased the number of hematopoietic colonies formed in a semisolid medium by AA marrows. Maximal colony numbers reached 30% of the numbers observed with normal bone marrow cells. Proliferation of AA cells cultured in a liquid medium containing SCF together with Epo, IL-3, GM-CSF, and G-CSF approached 70% of the control level, as measured by 3H-thymidine incorporation. The effect of the combination of SCF with the other growth factors was more than 10 times stronger than that of the growth factors alone. The most marked effect of SCF was on the generation of erythroid colonies by precursor cells. The results demonstrate synergism between CSF and other hematopoietic growth factors, resulting in the most efficient stimulation of the in vitro growth of AA bone marrow cells described to date. Use of SCF, either alone or in combination with other factors, may be of potential value in treatment of AA.
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PMID:Stem cell factor stimulates the in vitro growth of bone marrow cells from aplastic anemia patients. 137 45


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