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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)

Colony-stimulating factor-1 (CSF-1) is a specific haematopoietic growth factor that stimulates the production of macrophages by both bone marrow macrophage precursors (GM-CFC) and certain more mature peripheral tissue macrophages. The relationship of CSF-1 utilization and cell production by macrophage precursors at various stages of differentiation was studied. Bone marrow GM-CFC had the highest proliferative capacity followed by blood monocytes and peritoneal exudate macrophages (PEM) as determined by their cell doubling time (DT) which was also dependent on the concentrations of exogenous CSF-1. PEM had the longest initial lag period before commencing cell proliferation. Exogenous CSF-1 was constantly utilized by the growing cells; depletion of available CSF-1 resulted in growth arrest and, subsequently, cell death. The production of macrophage progeny, per amount of CSF-1, correlated with parent macrophage maturity; for each 100 U of CSF-1 consumed, bone marrow precursor cells and blood monocytes were capable of producing 17.9 x 10(4) and 13.4 x 10(4) progeny, respectively, whereas PEM generated only 4.6 x 10(4) daughter cells. Thus, the removal and destruction of CSF-1 by more mature, less proliferative tissue macrophages may provide a possible mechanism by which CSF-1 levels are reduced and the production of early haemopoietic macrophage precursors controlled.
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PMID:Delineation of receptor-mediated colony-stimulating factor (CSF-1) utilization and cell production by precursors of mononuclear phagocytic series at various stages of differentiation. 282 20

The effect of oxygen tensions in the physiological range as an environmental signal on the growth of in vitro murine hemopoietic progenitor cells and the production of hemopoietic growth factors (HGF) from macrophages was investigated. Early (BFU-E) and late (CFU-E) erythroid and granulocyte-macrophage (GM-CFC) progenitor cells were cultured in an atmosphere containing 2%, 3.5%, or 5% oxygen. For both the BFU-E and CFU-E populations, a gas phase containing 3.5% oxygen proved to be optimal, producing greater colony numbers than cultures incubated under 2% or 5% oxygen-tension conditions. For GM-CFC growth, 2% and 3.5% oxygen resulted in a greater stimulation than 5% oxygen. Macrophages derived from unseparated and unstimulated mouse bone marrow cells were cultured on hydrophobic Teflon foils under varying oxygen-tension conditions. The production of erythropoietin (epo), present in the culture supernatants, increased as the oxygen concentration increased from 2% to 3.5%, but then decreased as the oxygen concentration was increased further, from 3.5% to 5%. The presence of a factor demonstrating functional similarity with Interleukin-3 was produced optimally under 5% oxygen-tension conditions. The production of granulocyte-macrophage colony-stimulating factor (GM-CSF) was not significantly affected by changing the oxygen-tension conditions. These results demonstrate that physiological oxygen tension plays an important role not only in the growth of hemopoietic progenitor cells, but also as a physiochemical signal that macrophages can sense and respond to in order to regulate the production of specific secretory products.
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PMID:A role for the macrophage in normal hemopoiesis. II. Effect of varying physiological oxygen tensions on the release of hemopoietic growth factors from bone-marrow-derived macrophages in vitro. 309 86

Normal human bone marrow mononuclear cells were fractionated by differential adherence, immunomagnetic separation, and fluorescence-activated cell sorting (FACS). The resultant fractionated cells were cultured in semisolid medium to monitor the presence of BFU-E, Mix-CFC, and nonerythroid CFC. Two populations of cells were recovered on the basis of binding by the monoclonal antibody (MoAb) RFB-1. One of these populations contained BFU-E that were stimulated only by erythropoietin (Epo), whereas the second population contained BFU-E responsive to Epo, Epo and recombinant human granulocyte-macrophage colony-stimulating factor (rHGM-CSF), or Epo and human placental-conditioned medium (HPCM). Prior enrichment of clonogenic cells by removal of adherent and Leu-M3+ve, Leu-4+ve, Leu-7+ve, B1+ve, WEMG1+ve, and Glycophorin A+ve cells, followed by FACS fractionation on the basis of RFB-1 binding, consistently resulted in recoveries of BFU-E, Mix-CFC, and nonerythroid CFC of greater than 100% (up to 800%). These procedures also resulted in enrichment of up to 200-fold and frequencies of 1:6 for BFU-E, 1:5 for CFC, and 1:130 for Mix-CFC.
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PMID:Fractionation of subsets of BFU-E from normal human bone marrow: responsiveness to erythropoietin, human placental-conditioned medium, or granulocyte-macrophage colony-stimulating factor. 327 56

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has previously been shown to stimulate granulocyte, macrophage, and megakaryocyte lineages to act as an erythroid burst-promoting activity and to stimulate limited replication of spleen colony-forming cells. Here we demonstrate that murine GM-CSF alone or in combination with macrophage colony-stimulating factor (CSF-1) can stimulate colony-forming cells in bone marrow (BM) that have a high proliferative capacity. In cultures of BM from mice treated with 5-fluorouracil (FU) eight days before sampling, GM-CSF alone or in combination with CSF-1 stimulated the formation of large macrophage colonies with diameters greater than 0.5 mm. CSF-1 alone, at 800 units or greater, also stimulated larger colonies; however, these colonies were always less than 1.1 mm in diameter, whereas GM-CSF in combination with CSF-1 stimulated many colonies with diameters between 1 and 4 mm. At all doses of CSF-1 tested, the combination of factors resulted in a synergistic increase in colonies with diameters greater than 1.0 or 2.0 mm. Analysis of the incidence of colony-forming cells in the BM of normal mice and mice 2, 4, 6, and 8 days after FU treatment demonstrated that the progenitor cells stimulated by GM-CSF alone or in combination with CSF-1 were depleted by FU treatment in vivo and regenerated more rapidly than did the macrophage progenitors (M-CFC) stimulated by CSF-1 alone. This is similar to the properties of the previously described high-proliferative potential, colony-forming cell (HPP-CFC) that is responsive to interleukin-3 plus CSF-1 but not the HPP-CFC stimulated by hematopoietin 1 plus CSF-1. These data suggest that GM-CSF plus CSF-1 act synergistically to stimulate a population of progenitor cells that have a high proliferative potential and have properties similar to those of the population of HPP-CFC stimulated by interleukin-3 plus CSF-1.
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PMID:Stimulation of murine colony-forming cells with high proliferative potential by the combination of GM-CSF and CSF-1. 329 80

Antitumor chemotherapy is often limited by hematopoietic toxicity. In an attempt to determine if it is possible to attenuate the myelosuppressive effects of chemotherapy, we administered recombinant murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF), a multilineage hematopoietic growth factor, to mice receiving 5-fluorouracil (5-FU). Mice receiving injection of 5-FU followed 24 hr later by a single 1-microgram injection of rmGM-CSF had significantly increased femoral bone marrow granulocyte-macrophage colony-forming cells (GM-CFC) 48 hr after 5-FU injection compared to animals receiving 5-FU alone. Animals receiving rmGM-CSF twice daily beginning 24 hr after 5-FU had significantly elevated white blood cell counts and increased granulocyte and monocyte counts at Day 7 following 5-FU injection, compared to those of 5-FU animals. The total reserve of GM-CFC was also expanded initially in the femoral marrow and later in the spleen of animals receiving rmGM-CSF following 5-FU. A means of accelerating bone marrow recovery and restoration circulating granulocytes and monocytes could allow more frequent doses of chemotherapy to be administered or shorten the time period that patients are leukopenic.
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PMID:Recombinant granulocyte-macrophage colony-stimulating factor improves hematopoietic recovery after 5-fluorouracil. 329 40

Human bone marrow contains plastic-adherent hemopoietic progenitor cells whose plating efficiency is increased by brief (2 h) exposure to methylprednisolone (MP). When subsequently covered with methylcellulose medium, they form colonies of monoblastoid cells. Colony size, but not number, and mature cell production are increased by erythropoietin (epo) and granulocyte-macrophage colony-stimulating factor (GM-CSF). However, colonies do not grow under serum-free conditions. The resistance of plastic-adherent progenitors to treatment with 5-fluorouracil (5FU), their growth pattern, and their capacity to produce granulocytic and erythroid colonies on replating, suggest that they may be similar to the primitive, 5FU-resistant, plastic-adherent progenitor cells (HPP-CFC) in murine marrow.
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PMID:Plastic-adherent progenitor cells in human bone marrow. 360 80

Granulocyte-macrophage colony-stimulating factor (GM-CSF) production by the peripheral blood (PB) cells of hairy cell leukemia (HCL) patients whose PB contained only 2 to 10% hairy cells was studied in an in vitro bone marrow culture system. In addition, the possible inhibitory effect on the growth of normal granulocyte-macrophage colony-forming cells (GM-CFC) by the patients' mononuclear cells or serum was assayed. GM-CSF production by PB cells of HCL patients was 82 +/- 18% (mean +/- sd) lower than its production by normal PB cells. No significant inhibition of normal GM-CFC growth was observed in the presence of patients' PB mononuclear cells or their serum. These findings suggest that in HCL patients the monocyte-macrophage system is defective in its capacity to produce GM-CSF. This defect may play a role in the impaired granulocyte production known to occur in HCL.
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PMID:Hairy cell leukemia: defective production of granulocyte-macrophage colony-stimulating factor by peripheral blood cells. 698 26

Umbilical cord blood (CB) has been identified as a potential source of hematopoietic stem cells suitable for clinical transplantation. We used long-term cord blood cultures (LTCBC) to evaluate the hematopoietic potential of populations of umbilical CB cells phenotypically defined and isolated by flow cytometry. LTCBC initiated with CD34+HLA-DR+ and CD34+HLA-DR- CB cells were examined over a period of 8 weeks for the production of assayable burst-forming units-erythroid (BFU-E), colony-forming units-granulocyte/macrophage (CFU-GM), and colony-forming units-mixed (CFU-GEMM) in response to repeated additions of stem cell factor (SCF), interleukin-3 (IL-3), IL-6, and either erythropoietin (Epo) or granulocyte-macrophage colony-stimulating factor (GM-CSF). The LTCBC-initiating cell (LTCBC-IC) appeared to be present among CD34+HLA-DR+ cells, in contrast to our previous findings in adult bone marrow (BM), where the long-term culture initiating cells were shown to be CD34+HLA-DR-. In addition, production of BFU-E, CFU-GM, and CFU-GEMM in CB CD34+HLA-DR+ cells displaying low uptake of the supravital dye rhodamine 123 (Rh123) exceeded those detected in the fraction of cells with high uptake of Rh123. Furthermore, on day 21 of LTCBC, the production of the high proliferative potential colony-forming units (HPP-CFC) by CB CD34+HLA-DR+Rh123dull cells was five-fold greater than that detected in cultures initiated with their Rh123bright counterparts. Collectively, these data show that, contrary to what has been documented in adult human BM, LTCBC-IC and presumably CB cells capable of in vivo engraftment reside in the CD34+HLA-DR+Rh123dull fraction of CB. Although the functional significance of these differences between the in vitro behavior of phenotypically defined populations of CB and BM remains to be determined, these findings constitute an objective parameter with which the suitability of CB for clinical transplantation may be assessed.
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PMID:Evaluation of the in vitro behavior of phenotypically defined populations of umbilical cord blood hematopoietic progenitor cells. 750 62

We have previously shown that the most primitive human hematopoietic cells are included within a cell subpopulation expressing high levels of CD34 and low or undetectable levels of CD45RA and CD71. In this study, cord blood cells with this phenotype were sorted and further separated based on their expression on the Thy-1 antigen. The proliferation and differentiation of the purified cell fractions in response to a mixture of hematopoietic cytokines was analyzed in serum- and stroma-free liquid cultures. Thy-1+ cells (25% of CD34+ CD45RAlo CD71lo cells) were particularly enriched for high proliferative potential colony-forming cells (HPP-CFC; up to 45% of the clonogenic cells), whereas Thy-1- cells were enriched for multipotential colony-forming cells (CFU-MIX; up to 46% of the clonogenic cells). When both subpopulations were cultured in serum-free liquid cultures supplemented with a cytokine mixture that included steel factor, interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF)/IL-3 fusion protein, M-CSF, G-CSF, and erythropoietin, Thy-1+ cells showed a much higher numerical expansion of CD34+ cells (30,000-fold) and colony-forming cells (4,700-fold) than was observed in cultures initiated with Thy-1- cells (900-fold increase in CD34+ cell numbers and 241-fold increase in CFC numbers). Cells coexpressing CD34 and Thy-1 were only transiently expanded (up to 29-fold) and were not detected after day 22 of culture. When CD34+ CD45RAlo CD71lo Thy-1+ cells were cultured, either in semi-solid or liquid cultures, in the presence of anti-Thy-1 antibody, a significant reduction in progenitor cell numbers (particularly HPP-CFC) was observed. In contrast, CD34+ CD45RAlo CD71lo Thy-1- cells were not affected by anti-Thy-1. The results of this study indicate that Thy-1 is expressed on primitive cord blood progenitors with the highest in vitro proliferative potential, and further suggest that Thy-1 is involved in hematopoietic cell development, possibly by mediating a negative signal that results in inhibition of primitive cell proliferation.
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PMID:Thy-1 expression is linked to functional properties of primitive hematopoietic progenitor cells from human umbilical cord blood. 751 97

Previous work has shown that part of the hierarchical structure of the hematopoietic system can be described by HPP-CFC-1 (primitive high proliferative potential colony-forming cells responding to colony-stimulating factor-1 [CSF-1] + interleukin-3 [IL-3] + IL-1), HPP-CFC-2 (more mature HPP-CFC responding to CSF-1 + IL-3), and mature HPP-CFC responding to the single factors, CSF-1, granulocyte-macrophage colony-stimulating factor (GM-CSF), or IL-3. In this study, we have attempted to relate the murine HPP-CFC, stimulated by various combinations of growth factors (GFs)--CSF-1, GM-CSF, IL-3, IL-6, IL-1, stem cell factor (SCF), and transforming growth factor-beta (TGF-beta)--and by CSF-1, GM-CSF, and IL-3 on their own, to these known progenitors. Studies involving regeneration of the bone marrow after 5-fluorouracil (5-FU) treatment, generation of progenitors in liquid cultures in response to different GF combinations, and the HPP-CFC content of lineage-negative rhodamine-sorted bone marrow (BM) fractions have indicated that: 1. the combinations CSF-1 + IL-3 + IL-1 + SCF and CSF-1 + IL-3 + IL-1 + IL-6, and possibly CSF-1 + GM-CSF + IL-3 + IL-1, stimulate pre-HPP-CFC-1; 2. the combinations CSF-1 + IL-1 + GM-CSF, CSF-1 + IL-1 + IL-6, CSF-1 + IL-1 + SCF, CSF-1 + IL-3 + SCF, CSF-1 + IL-6 + SCF, and IL-3 + SCF, appear to overlap with the CSF-1 + IL-3 + IL-1 combination to stimulate the more mature cells of the HPP-CFC-1 compartment; 3. the combinations CSF-1 + GM-CSF, CSF-1 + IL-1, CSF-1 + IL-6, and CSF-1 + SCF may stimulate the more mature cells of the HPP-CFC-2 population, while the single factors CSF-1, GM-CSF, and IL-3, as suggested in other reports, may stimulate HPP-CFC that are more mature than the HPP-CFC-2; 4. the combinations IL-3 + IL-6 and SCF + IL-6 appear to stimulate HPP-CFC that overlap with the HPP-CFC-1 population, while those responding to the combination GM-CSF + TGF-beta overlap with the HPP-CFC-2 population within the hematopoietic hierarchy; and 5. CSF-1 and GM-CSF appear to be interchangeable in the combinations studied.
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PMID:The relationship between different high proliferative potential colony-forming cells in mouse bone marrow. 751 52


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