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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)

An increasing amount of data provides strong evidence for the complex multifactorial control of primary hemopoietic functions. Here we present a new multicellular functional unit, the Hematon, isolated from the light-density floating fraction of normal human bone marrow (BM) aspirates. The Hematon is organized in a compact, three-dimensional spheroid complex from central adipocytes, fibroblastoid cells, and resident macrophages that compartmentalize myeloid, erythroid, and megakaryocyte progenitor cells and their progenies. The Hematon fraction is more than twofold more abundant in progenitor cells when compared to the mononuclear cell (MNC) fraction as gauged by cytological techniques and by analysis of granulocyte-macrophage colony-forming unit (GM-CFU) populations. Individual Hematons may produce, within 2-3 weeks, up to 50,000 hemopoietic cells of different cell lineages in organotypic microcultures. Recombinant human hematopoietic growth factors interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and macrophage colony-stimulating factor (M-CSF) significantly stimulated the endogenous cell production of some but not all of the individually treated Hematons, indicating the heterogeneity of factor-responsive cells within the Hematon population. Comparative observations of 184 BM aspirates support the hypothesis that the presence of Hematons in a BM aspirate correlates positively with homeostatic blood cell production, because the Hematon was present in normal BM (31/40) and it was rare among patients with myelodysplastic syndromes (15/53), acute myeloblastic leukemia (7/39), and chronic myelocytic leukemia (5/52). We suggest that the Hematon represents a unifying model around which the variability of fundamental BM functions and dysfunctions can be explored.
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PMID:Hematon, a multicellular functional unit in normal human bone marrow: structural organization, hemopoietic activity, and its relationship to myelodysplasia and myeloid leukemias. 218 30

The promise of hematopoietic growth factors is now being realized as clinical trials become more mature. The uses of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor are now becoming more established in therapeutic applications of disease states. A variety of new hematopoietic growth factors is on the horizon, including recombinant human macrophage colony-stimulating factor (rhM-CSF), which has recently entered clinical trials after extensive preclinical testing. The diverse biological actions of rhM-CSF will provide novel ways of approaching various medical problems across the disciplines of hematology, oncology, infectious disease and cardiology.
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PMID:Preclinical and clinical evaluation of recombinant human macrophage colony-stimulating factor (rhM-CSF). 218 44

The AF1-19T rat cell line has been found to produce an activity that acts synergistically with colony-stimulating factor 1 (CSF-1) to stimulate primitive high proliferative potential colony-forming cells (HPP-CFC) in mouse bone marrow (BM) that appear to be the same as those stimulated by the combination of 5637-cell-conditioned medium (CM) plus CSF-1 or recombinant human (rh) interleukin 1 (IL-1) plus recombinant murine (rm) interleukin 3 (IL-3) plus CSF-1. AF1-19T also produced granulocyte-macrophage colony-stimulating factor (GM-CSF), which could be separated from this synergistic activity by gel filtration followed by hydroxylapatite chromatography. Results obtained from the mouse thymocyte costimulation assay for IL-1, the hybridoma growth factor assay for interleukin 6 (IL-6), the ability to stimulate HPP-CFC, and the ability to block this stimulation with an antibody to murine IL-1 alpha suggest that the synergistic activity in AF1-19T-CM is probably a mixture of IL-1 activity and IL-6 or an IL-6-like activity. Other workers have described a progenitor cell population in mouse BM (CFU-A) that forms large colonies in response to AF1-19T-CM plus CSF-1 or GM-CSF plus CSF-1. Experiments involving the kinetics of recovery after 5-fluorouracil treatment and generation of progenitors suggest that the GM-CSF-plus-CSF-1-responsive progenitors, and hence CFU-A, are a more mature cell type than the more primitive HPP-CFC, responsive to 5637-cell-CM plus CSF-1 or rhIL-1 plus rmIL-3 plus CSF-1.
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PMID:Progenitor cells in murine bone marrow stimulated by growth factors produced by the AF1-19T rat cell line. 218 22

We investigated the production of interleukin-3 (IL-3)-like factor by murine astrocytes. Supernatants from lipopolysaccharide (LPS)-stimulated astrocytes induced proliferation of IC-2, an IL-3- and granulocyte/macrophage colony-stimulating factor (GM-CSF)-dependent cell line. This activity was completely neutralized by the antibody against GM-CSF but not by the anti-IL-3 monoclonal antibody. Northern blot analysis revealed the expression of GM-CSF mRNA, but not of IL-3 mRNA, in cultured astrocytes. These results indicate that with proper stimuli murine astrocytes produce GM-CSF.
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PMID:Production of granulocyte/macrophage colony-stimulating factor by cultured astrocytes. 219 11

Proliferation of acute myelogenous leukemia (AML) derived blast cells requires the presence in culture of one or more growth factors. In the majority of cases Interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulate clonogenicity of AML blasts, which can be synergised by Interleukin-6 (IL-6), Interleukin-1 (IL-1) and granulocyte colony-stimulating factor (G-CSF). In contrast, macrophage colony-stimulating factor (M-CSF) favors deterministic divisions. A substantial part of AML samples have clonogenic cells which, however, proliferate autonomously in vitro. The production by leukemic cells of a variety of growth or synergizing factors including GM-CSF, G-CSF, IL-1, IL-6, and Tumor Necrosis Factor (TNF) has been demonstrated and a fraction of cases will use these molecules to support clonogenic growth in an autocrine or paracrine fashion. However, unlike the situation with retrovirus-induced murine or avian leukemias, the role of production of CSFs and other cytokines by human leukemic cells in the transformational process remains uncertain.
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PMID:Control of blast cell proliferation and differentiation in acute myelogenous leukemia by soluble polypeptide growth factors. 220 37

Mouse bone marrow cells in liquid culture with interleukin 3 generate nonadherent granulocytes, mast cells, and macrophages. The addition of 13-cis retinoic acid (13cRA) (10(-8)-10(-6) M) enhanced proliferation of the nonadherent cells, and concentrations greater than 5 x 10(-7) M stimulated a sixfold increase in adherent macrophages. Four-color flow cytometry was used to identify the lineages present using the following antibodies: MAC1 (granulocytes and macrophages), F4/80 (macrophages), B54.2 (mast cells), and H12 (anti-Thy1.2 to identify myeloid precursors). This analysis demonstrated a twofold increase in MAC1+ F4/80+ cells, which were sorted and identified morphologically as macrophages. 13cRA also increased by 60%-95% the numbers of colony-forming cells responsive to interleukin 3 (IL-3) and macrophage colony-stimulating factor (M-CSF) but did not significantly change the colony-forming cells responsive to granulocyte-macrophage colony-stimulating factor (GM-CSF). These data suggest that 13cRA increases the production of macrophages by modulating the commitment of IL-3-expanded progenitor cells to the macrophage lineage.
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PMID:13-cis retinoic acid augments the production of macrophages in mouse bone marrow cultures stimulated with interleukin 3. 220 41

The effects of recombinant cytokines on the ploidy of human megakaryocytes derived from megakaryocyte progenitors were studied using serum-free agar cultures. Nonadherent and T cell-depleted marrow cells were cultured for 14 days. Megakaryocyte colonies were identified in situ by the alkaline phosphatase anti-alkaline phosphatase technique, using monoclonal antibody against platelet IIb/IIIa. The ploidy of individual megakaryocytes in colonies was determined by microfluorometry with DAPI (4',6-diamidino-2-phenylindole) staining. Recombinant human interleukin 3 (rhIL-3) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) supported megakaryocyte colony formation in a dose-dependent manner. However, both rhIL-3 and rhGM-CSF had no definite ability to increase the ploidy values. Recombinant human erythropoietin (rhEpo) or recombinant human macrophage colony-stimulating factor (rhM-CSF) by itself did not stimulate the growth of megakaryocyte progenitors. rhEpo or rhM-CSF, however, stimulated increases in the number, size and ploidy values of megakaryocyte colonies in the presence of rhIL-3 or rhGM-CSF. Recombinant human interleukin 6 (rhIL-6) showed no capacity to generate or enhance megakaryocyte colony formation when added to the culture alone or in combination with rhIL-3. rhIL-6, however, increased the ploidy values in colonies when added with rhIL-3. These results show that rhEpo, rhM-CSF and rhIL-6 affect endomitosis and that two factors are required for megakaryocyte development.
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PMID:The effect of cytokines on the ploidy of megakaryocytes. 220 62

We have studied the ability of three different Mycoplasma species to induce proliferation of bone marrow-derived macrophages (BMM). We observed a significant mitogenic effect when BMM cells from BALB/c, DBA/2J, SJL, and C57BL/6 mice were incubated with membranes derived from Mycoplasma arginini or M. arthritidis but not when they were incubated with an equivalent amount of M. pulmonis membrane. We also determined that pretreatment of mycoplasma membrane preparations with papain eliminated the ability of these preparations to induce BMM proliferation. To determine whether these membrane fractions acted indirectly by stimulating the production of soluble factors known to stimulate proliferation of BMM cells, we performed blocking studies with antibodies directed against colony-stimulating factor 1 (CSF-1), interleukin-3 (IL-3), and granulocyte-macrophage colony-stimulating factor. Our results indicate that antibodies directed against either CSF-1 or IL-3 failed to block mycoplasma-initiated proliferation of BMM cells. However, when anti-GM-CSF was added to proliferative cultures at the time of initiation, we saw a dose-dependent reduction of mycoplasma-initiated proliferation. We conclude that the ability of mycoplasma membranes to initiate the proliferation of BMM is not shared by all species of mycoplasma and that it involves the production of GM-CSF by an as yet undetermined cell.
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PMID:Differential induction of bone marrow macrophage proliferation by mycoplasmas involves granulocyte-macrophage colony-stimulating factor. 222 27

Activated polymorphonuclear neutrophilic granulocytes (PMN) play an important role in propagation of inflammatory reactions and are capable of mediating tissue damage particularly by release of reactive oxygen species and lysosomal contents. Cytokines produced by monocytes as well as epidermal cells were recently shown to modulate PMN function. Therefore, the effect of immunomodulating cytokines on the oxidative metabolism of isolated human PMN was tested by functional as well as ultrastructural criteria. The following recombinant human cytokines were tested: tumor necrosis factor (TNF alpha), lymphotoxin (TNF beta), granulocyte-macrophage colony-stimulating factor (GM-CSF), M-CSF, G-CSF, PDGF, TGF-beta, interleukin-1 (IL-1) alpha and beta, IL-2, IL-3, IL-4, IL-5, IL-6, MONAP/MOC/NAF (IL-8), interferon-alpha and -gamma. Only TNF alpha, TNF beta and GM-CSF were found to be direct stimuli of the oxidative burst in human PMN whereas IL-3, IL-5, and IL-8 were active only at extremely high concentrations. None of the other cytokines tested induced any significant effect on isolated human PMN at physiological concentrations. The results clearly demonstrate that only selected cytokines are capable of inducing a long lasting activation of PMN oxidative metabolism. Release of these mediators represents a specific signal for PMN activation in inflammatory disease states.
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PMID:Activation of the oxidative metabolism in human polymorphonuclear neutrophilic granulocytes: the role of immuno-modulating cytokines. 225 41

In vivo diffusion chambers implanted in normal mice after 5 days of bone marrow cell culture contained precursor cells that in the presence of recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF), interleukin 3 (IL-3), or colony-stimulating factor 1 (CSF-1), alone or in combination, formed both small and large (high proliferative potential colony-forming cells, HPP-CFC) macrophage-containing colonies in vitro. Synergistic factor from serum-free 5637 cell-conditioned medium (SF5637) enhanced HPP-CFC colony growth only in cultures containing CSF-1. Higher numbers of CSF-1- plus IL-3-responsive colony-forming cells (HPP-CFC-2) were detected in diffusion chamber colony-forming unit (CFU-D) colonies than in intercolony areas, suggesting that they were derived from cells that give rise to the diffusion chamber colony. Further study demonstrated that CFU-D colonies contained cells that formed large macrophage-containing colonies (HPP-CFC-1) in CSF-1- plus SF5637-containing cultures. These findings suggest that single cells (CFU-D) forming colonies in diffusion chambers in mice can give rise to both HPP-CFC-1 and to cells probably representing their progeny, HPP-CFC-2.
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PMID:Relationship between cells forming colonies in diffusion chambers in vivo (CFU-D) and cells with high proliferative potential in vitro (HPP-CFC-1 and -2). 232 64


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