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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)

In the present study, culture supernatants from larger granular lymphocytes (LGL) that were activated with Candida albicans antigens were shown to stimulate the ability of neutrophils to inhibit fungal growth. Identification of the activation factors showed that granulocyte-macrophage colony-stimulating factor (GM-CSF), a hematopoietic growth factor, was involved. Human peripheral blood mononuclear cells were fractionated by Percoll density centrifugation and each subpopulation of cells was stimulated with C albicans yeast cells. GM-CSF was produced in those fractions enriched for LGL, but not T lymphocytes or adherent monocytes. Additionally, the phenotype of the GM-CSF-producing cell was found to be CD2+, CD16+, HLA-DR+, and negative for CD4, CD8, and CD15. Kinetic studies demonstrated that GM-CSF appeared in the supernatants within 2 days of culture and continued to be produced up to 7 days. Optimal stimulation of LGL was seen at a ratio of 3 heat-killed C albicans yeast cells per LGL. Thus, LGL play an important role in host defense against this opportunistic pathogen by producing cytokines, including GM-CSF, which in turn activates the fungicidal activity of neutrophils.
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PMID:Production of granulocyte-macrophage colony-stimulating factor by large granular lymphocytes stimulated with Candida albicans: role in activation of human neutrophil function. 202 83

Treatment of monocytes with recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) was shown to enhance their antimycobacterial activity in an in vitro assay. Furthermore, Mycobacterium avium-M. intracellulare was found to induce the production of this hemopoietic growth factor. Human peripheral blood mononuclear cells were fractionated by plastic adherence and Percoll density centrifugation, and each population of cells was stimulated with mycobacteria. GM-CSF was produced by both monocytes and large granular lymphocytes (LGL) but not T lymphocytes. The phenotype of the GM-CSF-producing LGL was found to be CD2+, CD16+, and HLA-DR+ but negative for T-cell and monocyte markers. Kinetic studies demonstrated that GM-CSF appeared in the supernatant fluids within 2 days of culture of either monocytes or LGL and continued to be produced up to 7 days of incubation. Northern (RNA) blot analysis of RNA from both cell types demonstrated the expression of GM-CSF message within 24 h of stimulation. From these studies, LGL and monocytes are capable of responding to M. avium-M. intracellulare by producing factors that augment normal immune functions, including the antibacterial capability of monocytes.
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PMID:Production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by monocytes and large granular lymphocytes stimulated with Mycobacterium avium-M. intracellulare: activation of bactericidal activity by GM-CSF. 205 Apr 5

Human eosinophils are known to lose Ia antigen expression as they mature, and, accordingly, eosinophils obtained from the blood of five eosinophilic donors and three of four normal donors failed to display the major histocompatibility complex class II antigen HLA-DR, as determined by flow cytometry. However, when eosinophils from these nine donors were maintained in culture with recombinant human granulocyte-macrophage colony-stimulating factor and murine 3T3 fibroblasts, HLA-DR consistently developed on the eosinophils. By days 4-6 of culture, 24-97% of eosinophils were HLA-DR+, and the eosinophils remained morphologically mature. In contrast, another class II antigen, HLA-DQ, was not detectable by flow cytometry on eosinophils from eight of nine donors. Cultured eosinophils were able to synthesize HLA-DR, as documented by the incorporation of [35S]methionine into immunoprecipitable HLA-DR heavy and light chains. These findings show that mature eosinophils can synthesize and express HLA-DR and provide a means whereby eosinophils may interact with CD4+ lymphocytes.
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PMID:Mature human eosinophils have the capacity to express HLA-DR. 291 83

Human T-lymphocyte lines that were selected for recognition of HLA-DR6 antigen and were dependent for growth in vitro on an added source of interleukin-2 (IL-2) were derived from the peripheral blood of normal individuals. Each was tested for production of a lymphokine(s) with properties of granulocyte-macrophage colony-stimulating factor (GM-CSF) using as target cells nonadherent cells from human long-term bone marrow cultures (LTBMC) or fresh marrow. Each of eight T-lymphocyte lines that were OKT3, OKT4, and HLA-DR positive produced GM-CSF that stimulated colony formation by both LTBMC cells and fresh marrow. Individually examined single-cell-derived bone marrow colonies growing in T-cell GM-CSF contained peroxidase-positive neutrophils, and macrophage-monocytes (GM-CFUc). Supernatant from a single-cell-derived T-cell clonal line designated F1 stimulated formation of granulocyte-macrophage colonies, megakaryocyte colonies, macroscopic erythroid bursts, and multipotential colonies containing erythroid cells, megakaryocytes, neutrophilic and eosinophilic granulocytes, and monocyte-macrophages (CFU-GEMM) in the presence of added erythropoietin. These data indicate that human IL-2-responsive T-lymphocytes produce lymphokine(s) that stimulate proliferation of primitive as well as committed hematopoietic stem cells, and implicate human T-lymphocytes in regulation of human multipotential hematopoietic stem cells in vivo.
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PMID:Production of colony-stimulating factor(s) for granulocyte-macrophage and multipotential (granulocyte/erythroid/megakaryocyte/macrophage) hematopoietic progenitor cells (CFU-GEMM) by clonal lines of human IL-2-dependent T-lymphocytes. 633 54

Multilineage differentiation of human fetal bone marrow CD34+ cell subsets was examined using a single-cell liquid culture assay. Four CD34+ cell populations, ie, (1) CD38-, HLA-DR+, (2) CD38-, HLA-DR-, (3) CD38+, HLA-DR-, and (4) CD38+, HLA-DR+ cells, were sorted as single cells into 96-well flat-bottom culture plates containing long-term culture medium supplemented with interleukin-3, interleukin-6, stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor, erythropoietin, basic fibroblast growth factor (bFGF), and insulin-like growth factor-1 (IGF-1). Single CD34+, CD38-, HLA-DR+ cells had the highest replating efficiency as well as the highest replating efficiency. The cellular composition of the single-cell progeny was studied by morphologic and/or flow cytometric examination. Only the progeny of single CD34+ cells that lacked CD38 could give rise to each of the hematopoietic cell lineages. The expansion of the progeny of single CD34+, CD38-, HLA-DR+ cells was examined in more detail and showed three clearly distinguishable growth patterns: 28% (SD, +/- 10%; n = 14) of the single cells formed cell clusters/colonies; 9% (SD, +/- 4%; n = 14) formed dispersed cells; and 11% (SD, +/- 6%; n = 14) gave rise to a mixture of cell clusters and dispersed cells. The dispersed cell growth pattern was reduced when SCF or bFGF and IGF-1 was absent in the growth factor cocktail. The replating ability of the dispersed cells was considerably larger than that of cells with other growth patterns, in that 76% of the cells that gave rise to dispersed cells and 54% of the cells that gave rise to dispersed cells as well as cell clusters gave rise to a second generation, but only 7% of the cells that gave rise to cell clusters gave rise to a second generation. The second generation of cells continued to produce third and fourth generations after repetitive replating, except for the replated cells from cell clusters. In contrast with the first-generation progeny, SCF did not have an influence on the replating ability of the cells. Only in the progeny of single CD34+, CD38-, HLA-DR+ cells that gave rise to dispersed cells was each of the hematopoietic cell lineages found, ie, B lymphocytes, neutrophils, monocytes, macrophages, osteoclasts, basophils/mast cells, eosinophils, erythrocytes, megakaryocytes, and platelets.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Lymphoid and myeloid differentiation of single human CD34+, HLA-DR+, CD38- hematopoietic stem cells. 751 Jan 44

High proliferative-potential colony-forming cells (HPP-CFC) have been identified in the bone marrow of mice and adult humans, and have been characterized as a compartment of primitive progenitors possibly including stem cells. In this report we describe the human fetal liver (FL) as a source of HPP-CFC. These FL HPP-CFC develop in clonal cultures in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) within 3 to 4 weeks. The median frequency of HPP-CFC in FL tissues between 16 and 21 weeks of gestational age was 1 in 3,000 total FL cells. After 4 weeks of growth, FL HPP-CFC grew to a median colony size of 8.3 x 10(4) cells/colony. Using cell-sorting techniques FL HPP-CFC were shown to be predominantly contained in the CD34+ CD33+ CD38- fraction of FL cells. FL HPP-CFC were heterogeneous for HLA-DR expression, and no differences in proliferative capacities were observed between HLA-DR+ and HLA-DR- HPP-CFC. The CD34+ CD33-HLA-DR- CD38- population, previously suggested to contain stem cells, was observed to be very rare in the FL, representing approximately 1 in 1.7 x 10(5) light-density FL cells and containing almost no CFC. Therefore, it is possible that stem cells are contained in the CD33+ fraction of FL cells. Phenotypic characterization of CD34+ CD33+ CD38- lin -LDFL cells showed that these cells are also CD13+, predominantly Thy-1+, CD45RA-, CD45RO-, CD71-, and heterogenoeous for c-kit expression. These data suggest that FL HPP-CFC represent a heterogeneous compartment of primitive myeloid progenitors that may include stem cells.
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PMID:Expression of CD33, CD38, and HLA-DR on CD34+ human fetal liver progenitors with a high proliferative potential. 751 3

ELF-153 is a cell line that has been established from a patient with a poorly differentiated acute myeloid leukemia associated with an acute myelofibrosis. A majority of cells had a blast morphology with the phenotype of a myeloid hematopoietic progenitor, ie, CD34+, CD33+, CD13+, HLA-DR+, but CD38-, and the remaining cells (5% to 10%) expressed platelet restricted proteins such as CD41, CD42, CD36, CD61, and von Willebrand factor; some of them were polyploid (up to 32N) and exhibited demarcation membranes and alpha granules. No erythroid or other lineage-specific markers were detected. Proliferation of ELF-153 cells was highly stimulated by interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor and to a lesser extent by stem cell factor and IL-6. In contrast, the cell line did not respond to erythropoietin, leukemia inhibitory factor, IL-7, IL-11, granulocyte colony-stimulating factor, and basic fibroblast growth factor. ELF-153 cells could be separated by flow cytometry into three discrete cell populations (CD34+/CD61-, CD34+/CD61+, and CD34-/CD61+) with different proliferative and endomitotic properties corresponding to distinct stages of the mega karyocyte (MK) differentiation. This MK differentiation, which involved a minority of ELF-153, could be increased in the presence of 5-azacytidine and phorbol ester, but could not be significantly modified by growth factors. By contrast, cytochalasin B dramatically induced polyploidization without differentiation. It is noteworthy that association of 5-azacytidine to cytochalasin B dramatically induced the production of polyploid MK cells. To understand the molecular mechanisms underlying this MK differentiation, the expression of GATA-1 and GATA-2 was investigated in subpopulations of ELF-153. A high level of GATA-1 and GATA-2 mRNA was only present in the CD61+ cells. Therefore, these two transactivating factors may play an important role in the MK differentiation of ELF-153. We conclude that ELF-153 might be an important tool to investigate the mechanisms by which transcription factors control differentiation of MK progenitors.
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PMID:Growth and differentiation of the human megakaryoblastic cell line (ELF-153): a model for early stages of megakaryocytopoiesis. 751 73

In this study we define hematopoietic stem cells (HSCs) as a population of cells that, when sorted as single cells, gives rise to both myeloid as well as lymphoid progeny. We sorted single cells from four populations of CD34+ cells from fetal bone marrow: (1) CD38- HLA-DR-, (2) CD38- HLA-DR+, (3) CD38+ HLA-DR-, and (4) CD38+ HLA-DR+ into liquid culture media supplemented with interleukin-3 (IL-3) IL-6, stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor, erythropoietin, basic fibroblast growth factor (bFGF) and insuline-like growth factor (IGF-1). The HSCs were found in the cell populations lacking CD38, the plating efficiency was highest in the CD34+ CD38- HLA-DR+ cell population (48% n = 12); however, only a small proportion of the CD34+ CD38- HLA-DR+ cells showed both lymphoid and myeloid growth potential. When the identical cell populations were sorted into liquid culture media supplemented with bFGF and IGF-1, cell growth was noted from only 1%-5% of the sorted CD34+ CD38- HLA-DR- cells. The cells have the potential to grow and differentiate in vitro to form complex structures that recapitulate normal bone formation. Serial passages of the progeny from these cultures resulted in the formation of similar structures.
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PMID:Analysis of bone marrow stem cell. 752 79

The aim of this study was to identify markers specific for granulo-monocytic commitment of progenitor cells. Large panels of antibodies were screened for selective staining of subsets of CD34+ cells from fetal and adult bone marrow. Flow cytometric analysis showed that CD64/fc gamma RI was undetectable on noncommitted progenitor cells (CD34++, CD38-/lo, HLA-DR+) and expressed on a subset of lineage-committed progenitors (CD34+, CD38+) with higher mean orthogonal light scatter than the remaining CD34+ cells. The CD34+, CD64+ cells were CD19- and the majority were CD45RA+, CD71lo, suggesting that CD64 recognized granulomonocytic progenitor cells. Specificity of CD64 for the granulo-monocytic lineage was shown by demonstrating that colonies arising from CD34+, CD64+ cells consisted of 98% +/- 2% colony-forming unit-granulocyte-macrophage (CFU-GM) in semisolid medium containing stem cell factor (SCF), interleukin-3 (IL-3), IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin (EPO). In contrast, 63% +/- 15% of the colonies from the CD34+, CD64- cells were burst-forming unit-erythroid/colony-forming unit-erythroid (BFU-E/CFU-E). Furthermore, four-color immunofluourescence and cell sorting was used to analyze the progeny of cells cultured in liquid medium containing identical cytokines as used in the semisolid medium. This analysis showed that CD34+, CD64+ cells gave rise to 83% +/- 10% granulo-monocytic cells whereas progeny of the CD34+, CD64- cells contained 81% +/- 11% erythroid cells. Neutrophils as well as basophils and monocytes/macrophages were present in the cultures from CD34+, CD64+ cells, showing that this population contains progenitors of most types of granulo-monocytic cells. Two widely used myeloid markers, CD13 and CD33, were not myeloid-specific, because both were clearly positive on noncommitted progenitor cells. Of 40 antigens tested, CD15 was the only other marker fulfilling the criteria of a myeloid-specific marker. However, at concentrations of CD15 that did not induce aggregation, CD15+ cells constituted less than 50% of the CD34+, CD64+ cells. Furthermore, the CD34+, CD15- cells showed more than 50% higher CD34 mean fluorescence intensity than the CD64+, CD15+ cells, indicating that CD64 appears earlier than CD15 during differentiation. Thus, among a large number of antigens screened, CD64 was the most useful for the identification and purification of granulo-monocytic progenitor cells.
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PMID:CD64/Fc gamma RI is a granulo-monocytic lineage marker on CD34+ hematopoietic progenitor cells. 753 12

Preliminary studies in allogeneic BMT suggest that recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) is well tolerated. This is a prospective, multicenter, randomized, double-blind, placebo-controlled trial. Yeast-derived rhGM-CSF 250 micrograms/m2/day or placebo was administered by 4-hour i.v. infusion starting on the day of marrow infusion (day 0) to day 20. All patients received HLA-identical sibling marrow and cyclosporine and prednisone for GVHD prophylaxis. Fifty three patients received rhGM-CSF and 56 received placebo. Comparison of demographics revealed no differences. The time to achieve an absolute neutrophil count of > 0.5 x 10(9) cells/l was shortened in rhGM-CSF treated patients (day 13 vs. 17, P = 0.0001). The incidences of grade III-IV mucositis and infection were significantly reduced (P = 0.005, P = 0.001, respectively) and duration of hospitalization was modestly shortened by 1 day (P = 0.02) in rhGM-CSF treated patients. No differences in platelet recovery, erythrocyte recovery, incidence of veno-occlusive disease, GVHD severity, relapse or survival were observed. In conclusion, rhGM-CSF is well tolerated and reduces post-transplant morbidity in patients undergoing HLA-identical allogeneic BMT.
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PMID:Phase III randomized, double-blind placebo-controlled trial of rhGM-CSF following allogeneic bone marrow transplantation. 758 Oct 96


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