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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 59 (1992), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Astrocytes have the ability to secrete colony-stimulating factor 1 (CSF-1), a growth factor known to stimulate the proliferation of brain macrophages. We have studied the effect of cytokines such as interleukin 1 (IL-1), tumor necrosis factor-α (TNFα), and interleukin 6 (IL-6) on the production of CSF-1 by cultured primary astrocytes and an astrocytic cell line derived from embryonic mouse brain. We observed that both TNFα and IL-1 increased CSF-1 mRNA and protein levels in the astrocytic cultures. In contrast, IL-6 was ineffective. The CSF-1 mRNA levels were strongly reduced by incubating immortalized astrocytic cells with staurosporine, a protein kinase C inhibitor, both in the absence and in the presence of cytokines. Conversely, 12-O-tetradecanoylphorbol 13-acetate, a protein kinase C activator, increased CSF-1 mRNA levels. These results suggest a mechanism whereby mononuclear phagocytes could favor their own recruitment in the CNS by producing cytokines.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Fig. 1 Identification of CSF-1 mRNA by Northern blotting. Methods. Total L cell or C3H/HeJ mouse RNA was extracted8 and 40 jxg subjected to Northern blotting9'10. Blots were probed with the insert of a 2.3-kb cDNA clone to murine CSF-1 mRNA (pGEM2mCSF-53), containing the entire coding sequence ...
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-7217
    Keywords: CSF-1 ; serum markers ; breast cancer ; cytokines ; prognosis ; metastasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Earlier results [1], suggesting an autocrine tumor cell stimulation by CSF-1, are in agreement with data by Fildermannet al. [2], showing an enhanced motility and invasiveness in the CSF-1 receptor expressing BT20 breast cancer cell line upon stimulation with recombinant CSF-1. Tumor-cell secreted CSF-1 has also been shown to cause monocyte recruitment, but not cytotoxicity [3]. Down-regulation of monocyte class II antigen expression after exposure to high concentrations of CSF-1 [4] may decrease macrophage-mediated tumor cytotoxicity and favor tolerance. Raised CSF-1 serum levels may thus increase tumor metastatic behavior as well as cause immune suppression in advanced stage disease. We set out to evaluate serum CSF-1 levels in primary and metastatic breast cancer. Serum samples from one hundred and eighteen primary breast cancer patients and seventy-five patients with metastatic disease were assayed by radio-immuno-assay (RIA) for circulating colony-stimulating factor 1. Mean serum levels were significantly higher in the metastatic population (9.7 ng/ml ± 0.8) as compared to the patients with primary tumors (4.2 ± 0.2) (p = 0.0001). Patients with early stage tumors (T0/T1/T2) had significantly lower levels than patients with tumors of larger size (T3/T4) (p = 0.0001). Relapse and survival statistics were analyzed using Kaplan-Meier estimates. Samples from 118 primary breast cancer patients were available to study. The median follow up was 85 months (range: 1–108). An elevated CSF-1 concentration (〉 6.6 ng/ml or 〉 550 Units/ml) was associated with a shorter disease free interval (p = 0.03). In a multivariate analysis, including T (clinical tumor size), N (clinical node status), histological grade, and hormone receptor status, CSF-1 remained significantly associated with a poorer outcome (relative risk of relapse: RR: 3.3 [1.3–8.5]), together with tumor size (RR: 2.8[1–8.2]) and clinically involved nodes (RR: 4.1[2.1–8]). These results were not modified following adjustment for type of treatment. We conclude that raised circulating CSF-1 levels may be an indicator of early metastatic relapse.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 122 (1985), S. 221-228 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: CSF-1 is a hemopoietic growth factor that specifically regulates the survival, proliferation, and differentiation of mononuclear phagocytic cells. Populations of adherent bone marrow-derived macrophages (BMM) devoid of CSF-1 producing cells were used to study regulation by CSF-1 of macrophage entry into S phase. More than 95% of BMM possess the CSF-1 receptor. It was shown that 93-98% of BMM are cycling (S phase 8-9 hr, doubling time 24-28 hr) when cultured in the presence of CSF-1. BMM incubated with 15% FCS in the absence of CSF-1 or in the presence of CSF-1 concentrations inducing survival without proliferation enter a quiescent state. This state is characterized by a reduction in the synthesis of DNA (98%), total protein (35%), ribosomal protein (76%), and histone (96%) compared with the synthetic rate of these components in exponentially growing cells. Addition of CSF-1 to BMM rendered quiescent by removal of CSF-1 stimulated entry into S phase with a lag period of ∼12 h. This lag period is reduced to 8 hr in BMM made quiescent at concentrations of CSF-1 inducing survival without proliferation, an effect which may be related to the expected higher protein content of these cells (Tushinski and Stanley, J. Cell. Physiol., 116:67-75). Neutralization of CSF-1 by antibody at different times during the lag period indicates that CSF-1 is required for almost the entire lag period for the entry of any cells into S phase. In BMM rendered quiescent by removal of both serum and CSF-1, purified CSF-1 without serum stimulated entry of cells into S phase, whereas serum alone was ineffective. The results are consistent with a primary regulatory role of CSF-1 in mononuclear phagocyte proliferation, survival, and function.
    Additional Material: 4 Ill.
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  • 5
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 130 (1987), S. 420-427 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The SV40 transformed murine macrophage cell line, BAC1, proliferates in response to the colony stimulating factor, CSF-1 (Schwarzbaum et al., J. Immunol., 132:1158, 1984). In order to obtain a cell line suitable for biochemical and genetic studies of CSF-1 signal transduction, clones of BAC1 were established. Clones ranged from being completely autonomous to being completely dependent on CSF-1 for growth. Cells of one clone (2F5), which proliferated in response to either CSF-1 or granulocyte-macrophage CSF (GM-CSF) were characterized in detail. The kinetics of receptor-mediated internalization and intracellular destruction of CSF-1 were comparable to the kinetics observed with peritoneal exudate macrophages. CSF-1 was shown to regulate cell spreading, cell survival, protein degradation, and the duration of the G1 and S phases of the cell cycle. The 2F5 clone therefore exhibits a number of CSF-1 stimulated responses and is being used for genetic and biochemical studies of CSF-1 action.
    Additional Material: 7 Ill.
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  • 6
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 122 (1985), S. 362-369 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: A new approach, based on the occurrence of receptors for the mononuclear phagocyte lineage specific hemopoietic growth factor (HGF) colony stimulating ractor-1 (CSF-1) on developmentally early multipotent cells, is utilized to detect and assay rapidly another HGF, hemopoietin-2. This method is also used to determine the relative maturity of hemopoietin-2 target cells, to investigate synergism between hemopoietin-2 and CSF-1, and to measure CSF-1 receptor levels on maturing cells. While the target cell specificities of hemopoitin-2 and CSF-1 overlap, hemopoietin-2 causes the appearance of developmentally earlier 125I-CSF-1 binding cells de novo in the absence of CSF-1. Increased CSF-1 receptor densities are observed on cells incubated with either HGF, consistent with acquisition of the capacity for increased expression of the receptor by mononuclear phagocyte progenitor cells just prior to their differentiation to adherent mononuclear phagocytes. Together, both HGFs have a synergistic effect on the generation of 125I-CSF-1 binding cells with elevated CSF-1 receptor densities. Preliminary characterization of hemopoietin-2 from medium conditioned by WEHI-3 cells indicates that it is very similar to, if not identical with, interleukin-3 (IL-3) and the HGF(s) acting on multipotential cells and cells giving rise to erythroid cells, granulocytes, mononuclear phagocytes, and megakaryocytes. Purified IL-3 was shown to possess hemopoietin-2 activity.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 122 (1985), S. 370-378 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The preceding paper describes a new approach to the detection and assay of growth factors for developmentally early multipotent hemopoietic cells (Bartelmez et al., J. Cell. Physiol., 1985). This approach, involving measurement of the increase in the number of receptors for the mononuclear phagocyte specific hemopoietic growth factor (HGF), colony stimulating factor-1 (CSF-1), in cultures of developmentally early murine cells incubated with putative HGFs, has been used to define and assay hemopoietin-1. Hemopoietin-1 (Mr ∼ 20,000) is found in the medium derived from serum-free cultures of cells of the human urinary bladder carcinoma line 5637. In contrast to both hemopoietin-2 and CSF-1, which also stimulate an increase in CSF-1 receptor numbers in cultures of developmentally early hemopoietic cells, hemopoietin-1 alone has no detectable effect. However, hemopoietin-1 exhibits dramatic synergism wth CSF-1. In the presence of CSF-1, hemopoietin-1 stimulates the proliferation of developmentally earlier cells than those that respond to either CSF-1 alone or hemopoietin-2 alone or their combination. These cells proliferate for at least 3 days with no alteration of the average CSF-1 receptor density. However, by 5 days of incubation, the progeny of developmentally early hemopoietic cells that have proliferated in response to hemopoietin-1 + CSF-1 exhibit an approximately tenfold increase in the average CSF-1 receptor density per cell, which immediately precedes their differentiation to adherent mononuclear phagocytes. As hemopoietin-1 does not possess colony stimulating or burst promoting activities for murine bone marrow cells, but acts on multipotent hemopoietic cells, the analysis of the mechanism of its synergistic effects with HGFs such as CSF-1 are of special relevance to the regulation of early events in hemopoiesis.
    Additional Material: 6 Ill.
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  • 8
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 31 (1986), S. 203-216 
    ISSN: 0730-2312
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The binding and uptake of the colony-stimulating factor CSF-1 by peritoneal exudate macrophages (PEM) from lipopolysaccharide insensitive C3H/HeJ mice was examined at 2°C, and at 37°C. At 2°C, 125I-CSF-1 was bound irreversibly to the cell surface. At 37°C, 90% of the cell surface associated 125I-CSF-1 was rapidly internalized and subsequently degraded and the remaining 10% dissociated as intact 125I-CSF-1. Thus classical equilibrium or steady state methods could not be used to quantitatively analyze ligand-cell interactions at either temperature, and alternative approaches were developed. At 2°C, the equilibrium constant (Kd ≤ 10-13M) was derived from estimates of the rate constants for the binding (kon ≃ 8 × 105M-1s-1) and dissociation (koff ≤ 2 × 10-7s-1) reactions. At 37°C, the processes of dissociation and internalization of bound ligand were kinetically competitive, and the data was formally treated as a system of competing first order reactions, yielding first order rate constants for dissociation, koff = 0.7 min-1 (t1/2 = 10 min) and internalization, kin = 0.07 min-1 (t1/2 = 1 min). Approximately 15 min after internalization, low-molecular weight 125I-labeled degradation products began to appear in the medium. Release of this degraded 125I-CSF-1 was kinetically first order over three half-lives (Kd = 4.3 × 10-2 min-1, t1/2 = 16 min). Thus CSF-1 binds to a single class of receptors on PEM, is internalized with a single rate limiting step, and is rapidly destroyed without segregation into more slowly degrading intracellular compartments.
    Additional Material: 5 Ill.
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  • 9
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 31 (1986), S. 259-269 
    ISSN: 0730-2312
    Keywords: CSF-1 ; CSF-1 receptor ; mononuclear phagocytes ; membrane proteins ; colony-stimulating factor ; murine macrophages ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The colony-stimulating factor, CSF-1, selectively stimulates the survival, proliferation, and differentiation of mononuclear phagocytes. The solubilization, assay, and characteristics of the CSF-1 receptor from the J774.2 murine macrophage cell line are described. The recovery of cell-surface receptor in the postnuclear supernatant membrane fraction of hypotonically disrupted cells was 76%. Recovery of the ligand binding activity of the receptor after solubilization of this fraction with 1% Triton X-100 was ∼ 150%. The binding of 125I-CSF-1 to intact cells and membrane preparations was consistent with the existence of a single class of high-affinity receptor sites. In contrast, the equilibrium binding of 125I-CSF-1 to the solubilized postnuclear fraction indicated the existence of two distinct classes of binding site (apparent Kds 0.15 nM and 10 nM). A rapid assay was developed for the high-affinity sites, which were shown to be associated with the CSF-1 receptor. The function of the low-affinity sites, which have not been demonstrated on intact cells or cell membranes and which are 13 times more abundant than the high-affinity sites, is unknown. The solubilized high-affinity receptor-CSF-1 complex was stable on storage at 0°C and -70°C but dissociated at 37°C. Dissociation also occurred at 0°C in buffers of low pH (4.0) or high ionic strength (0.7 M NaCl).
    Additional Material: 4 Ill.
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