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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)

Studies on the effect of the microenvironment on hematopoiesis would benefit from the availability of pure populations of nontransformed cells of each of the stromal cell types. The adherent murine bone marrow stromal cell population in this study consisted of fibroblasts, endothelial cells, and macrophages. Fibroblasts were segregated from the phagocytic endothelial cells and macrophages by allowing the phagocytic cells to ingest magnetic beads, with subsequent exposure to a magnetic field, effecting cell separation. Pure colony cultures of fibroblasts and endothelial cells were formed by varying the bead-to-cell ratio and incubation period of the cells. For complete purification of the fibroblasts, subsequent passaging was also necessary. Near confluent growth of each type was obtained with subsequent passages and sustained culture. The cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) was used to enhance endothelial cell growth. We were not able to obtain pure populations of bone marrow macrophages in near confluent culture. The three cell types were identified by cellular morphology, acid and alkaline phosphatase staining, binding with the lectins Ulex europaeus and Bandeiraea simplicifolia, and the capacity to stain for the factor VIII-related antigen (von Willebrand's Factor).
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PMID:A method to establish pure fibroblast and endothelial cell colony cultures from murine bone marrow. 220 58

Conditioned medium (CM) obtained from a human hepatoma cell line, SK-HEP-1, contains colony-stimulating factors (CSFs) active on murine and human bone marrow-derived granulocyte and macrophage colony-forming units (CFU-GM) and a factor capable of inducing granulocyte-macrophage differentiation (GM-DF) of murine myelomonocytic leukemic cells WEHI-3B(D+) and human promyelocytic leukemic cells HL-60 when assayed in semisolid agar cultures. The human active granulocyte-macrophage colony-stimulating factor (GM-CSF) for day 7 CFU-GM and the GM-DF for WEHI-3B(D+) and for HL-60 are not separable by acrylamide agarose column chromatography, eluting at an apparent molecular weight between 20,000 and 35,000 daltons, or by isoelectric focusing (isoelectric point, pH 5.4). In addition, SK-HEP-1 CM contains erythroid burst-promoting activity (BPA) and a factor that promotes the growth of human mixed colonies. SK-HEP-1 cells, which grow as an adherent monolayer, appear not to be endothelial or monocytic in origin since by immunofluorescent staining they are negative for Ia (HLA-DR), monocyte antigen 1 and 2, lysozyme, and factor VIII-related antigen. Positive immunofluorescent staining for keratin and fibronectin suggests the possibility that SK-HEP-1 is an epithelial cell line. Constitutive production of GM-DF as well as other hematopoietic activities including GM-CSF, erythroid BPA, and an activity that promotes the growth of human mixed colony progenitors by a human epithelial tumor cell line, SK-HEP-1, suggests that this cell line is a valuable resource for both large-scale production of these factors and the cloning of the gene(s) that code for these regulators.
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PMID:Constitutive production of leukemia differentiation, colony-stimulating, erythroid burst-promoting, and pluripoietic factors by a human hepatoma cell line: characterization of the leukemia differentiation factor. 299 Jun 10

We established a human bone marrow stromal cell line (Saka) by infecting marrow adherent cells from semisolid marrow cultures with a recombinant simian virus-40 (SV40) virus. The cells expressed SV40 large tumor antigen, had a fibroblast-like shape, and expressed fibronectin and vimentin. They did not contain detectable alkaline phosphatase activity; express myeloid, lymphoid, or factor VIII-associated antigens; or develop adipocyte-like characteristics with dexamethasone treatment. Polymerase chain reaction analysis of Saka cell RNA detected expression of messenger RNAs for interleukin-6 (IL-6), IL-1 beta, granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, stem cell factor, and the 1,25-dihydroxyvitamin D3 receptor. Coculture of Saka cells with human marrow mononuclear cells enhanced formation of osteoclast-like multinucleated cells (MNC) in long term human bone marrow cultures. These MNC expressed calcitonin receptors and formed resorption lacunae on dentine. In contrast, coculture of marrow mononuclear cells with other SV40-transformed human marrow stromal cell lines did not increase MNC formation. Conditioned medium from Saka cells or coculture of bone marrow and Saka cells separated by a Millipore membrane did not enhance MNC formation. Addition of a neutralizing antibody to IL-6 or IL-1 beta blocked the effects of Saka cells on MNC formation. These results suggest that marrow stromal cells enhance osteoclast formation in part through direct cell to cell contact and production of IL-6 and/or IL-1 beta.
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PMID:Development and characterization of a human marrow stromal cell line that enhances osteoclast-like cell formation. 753 99

One representative of a number of severe lesions that occur outside the glomerular capillaries and involve podocytes is crescentic glomerulonephritis. The question of whether the crescent-forming cells are derived from glomerular epithelial cells or monocytes/macrophages is highly controversial and has not yet been clarified. To investigate the pathophysiology of podocytes in crescentic glomerulonephritis, we attempted to establish methods for culturing cells confirmed to be derived from podocytes, focusing particularly on the relationship between podocytes and macrophages. Nonadherent cells of unknown origin that grew from normal rat isolated glomerular cultures increased in number, reaching a total of 3.5 x 10(5)/ml on Day 11. They showed several characteristics of macrophages, the expression of specific antigens and enzymes, morphology, and production of H2O2. They expressed Fx1A but lacked the expressions of Thy1.1 or factor VIII. A morphologic kinetic study on Days 3 to 11 of culture showed that the cells with foot processes on the glomerular basement membrane changed into macrophagic cells (MC) and migrated from the glomeruli. Immunofluorescence double staining indicated that the cells that migrated from the glomerular surface on Day 8 were both anti-podocalyxin- and ED-1-positive. Furthermore, immunoelectron microscopy revealed that the ED-1-positive cells were located on the glomerular basement membrane. Pretreatment with anti-macrophages and -Thy1.1 antibodies, both with complement, did not reduce the number of MC, whereas pretreatment with puromycin aminonucleoside predominantly reduced the number of MC. A predominant decrease in the number of glomerular macrophages by gamma-irradiation did not result in a reduction of the number of MC. MC derived from glomerular cultures of bone marrow chimeric rats expressed the la antigen originated from recipient, which indicates that MC is not derived from bone marrow cells. Macrophage colony-stimulating factor accelerated the speed of the change into MC, and granulocyte-macrophage colony-stimulating factor dramatically enhanced its degree with increase of cell number on Day 8. We concluded that podocytes change into MC in normal rat glomerular culture and that the change is enhanced by colony-stimulating factors. The results provide a completely new insight into the origin of crescent-forming cells.
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PMID:Macrophagic cells outgrowth from normal rat glomerular culture: possible metaplastic change from podocytes. 894 Dec 17

In the course of normal embryogenesis, embryonic stem (ES) cells differentiate along different lineages in the context of complex three-dimensional (3D) tissue structures. In order to study this phenomenon in vitro under controlled conditions, 3D culture systems are necessary. Here, we studied in vitro differentiation of rhesus monkey ES cells in 3D collagen matrixes (collagen gels and porous collagen sponges). Differentiation of ES cells in these 3D systems was different from that in monolayers. ES cells differentiated in collagen matrixes into neural, epithelial, and endothelial lineages. The abilities of ES cells to form various structures in two chemically similar but topologically different matrixes were different. In particular, in collagen gels ES cells formed gland-like circular structures, whereas in collagen sponges ES cells were scattered through the matrix or formed aggregates. Soluble factors produced by feeder cells or added to the culture medium facilitated ES cell differentiation into particular lineages. Coculture with fibroblasts in collagen gel facilitated ES cell differentiation into cells of a neural lineage expressing nestin, neural cell adhesion molecule, and class III beta-tubulin. In collagen sponges, keratinocytes facilitated ES cell differentiation into cells of an endothelial lineage expressing factor VIII. Exogenous granulocyte-macrophage colony-stimulating factor further enhanced endothelial differentiation. Thus, both soluble factors and the type of extracellular matrix seem to be critical in directing differentiation of ES cells and the formation of tissue-like structures. Three-dimensional culture systems are a valuable tool for studying the mechanisms of these phenomena.
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PMID:Multilineage differentiation of rhesus monkey embryonic stem cells in three-dimensional culture systems. 1274 23

Antibodies develop to varying degrees during treatment with human proteins, including insulin, growth hormone, granulocyte-macrophage colony-stimulating factor, factor VIII, erythropoietin, and interferons. These antibodies may reduce the clinical efficacy of these agents by blocking or neutralizing their biologic activity and may have other biologic effects. For example, antibodies develop in 20 % to 40% of patients with severe hemophilia treated with human factor VIII; the presence of these antibodies can result in tolerance to the clotting effects of this agent. Similarly, a proportion of patients treated with interferon alpha develop antibodies, which inhibit its therapeutic effects. Therefore, it is important to test for neutralizing antibodies during treatment with these agents, particularly in patients who are unresponsive to treatment or have breakthrough disease. This article reviews the incidence and clinical impact of antibodies that develop in response to some of the commonly used protein therapeutic agents.
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PMID:Immunogenicity of recombinant human proteins: causes and consequences. 1526 6

Interferons are generally recognised as the treatment of choice in some infectious diseases, such as chronic hepatitis B and C. Since the early clinical trials it was documented that the therapeutic use of interferons could be complicated by the development of antibodies able to neutralise or to bind to the interferon molecule. This finding is not surprising if one considers that natural or therapy-induced antibodies to interleukin (IL)-1, IL-2, IL-6, IL-10, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, insulin and recombinant factor VIII have been reported in humans. Since hormones, cytokines, biological response modifiers and homeostatic agents are being used for the therapeutic management of many infectious, autoimmune and neoplastic diseases, the possibility that therapy-induced antibodies can develop in humans should be considered. In this article we summarise what is currently known about the clinical significance of antibodies to interferons in interferon-treated patients. The presence of circulating antibodies may affect the response to interferon. Antibody development may be clinically significant, depending on the titre and the time of appearance. In particular, the response to interferon therapy may be affected by antibodies when they appear early in therapy and at high titre.
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PMID:What is the practical significance of antibodies to interferons? 1802 May 59