Role of cyclic nucleotides in the proliferation of committed granulocyte-macrophage progenitor cells.
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Binding Sites↗
SEARCH · PubMed Health
Results for “Granulocyte Colony-Stimulating Factor”
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Type C RNA virus production and cell competence for normal differentiation in myeloid leukaemic cells.
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Antigens, Viral↗
Growth enhancement and serum replacement in cloning of murine mastocytoma and granulocyte/macrophage precursor cells: two distinct activities present in hemolysates.
In the present study we investigated the serum replacing and enhancing activities of erythrocyte lysates, obtained from different animal species, on the growth of murine mastocytoma cells and normal granulocyte/macrophage precursor cells (CFU-C) present in bone marrow. The soft agar technique for cloning hemopoietic cells in vitro was used to quantitate the growth of these cells in culture. Rat, rabbit, guinea pig, mouse and sheep hemolysates were tested for their capacity to replace or to enhance serum as a growth promoter. All hemolysates except mouse were able to replace serum efficiently when mastocytoma cells were cloned. On the other hand, only rat hemolysate proved to be efficient for cloning normal murine CFU-C. Since increasing the concentration of hemolysates in the soft agar medium did not change these results, the differences in activity are unlikely to reflect quantitative variations. However, hemolysates with little or no serum replacing capacity enhanced the clonal growth of normal CFU-C when added to small amounts (2.5%) of horse serum. Trypsin treatment of rat hemolysate destroyed its serum replacing capacity but not its enhancing activity. No correlation was found between the amount of hemoglobin and the replacing activity of each hemolysate. The data obtained in the present study point to the presence of at least two distinct activities in hemolysate: serum replacing and growth enhancing capacities.
Animals↗
Regulation of lipopolysaccharide-induced granulopoiesis and macrophage formation by spleen cells. I. Relationship between colony-stimulating factor release and lymphocyte activation in vitro.
Addition of bacterial lipopolysaccharide (LPS), a B cell mitogen, to mouse spleen cultures strongly stimulated production of colony-stimulating factor (CSF), the humoral regulator of granulopoiesis, and macrophage formation in vitro. Secretion of CSF from LPS-stimulated spleen cells coincided with cellualr DNA synthesis and cell transformation and both activities could be attributed to the lipid A moiety of the molecule. Different experimental approaches were used to study the relationship of CSF release and lymphocyte activation in response to LPS: a) modification of LPS with polymyxin B, an antibiotic bactericidal for most Gram-negative bacteria, caused a marked reduction in mitogenic activity, although the ability to induce CSF was not significantly altered; b)spleen cells from CBA/N mice, a mutant strain with an x-linked genetic defect in immunologic and mitogenic responses to polyclonal activators including LPS, showed diminished mitogeinc responses; however, high levels of CSF were produced; c) mitotic and DNA inhibitors (colchicine and cytosine arabinoside) did not affect CSF release although they completely inhibited mitogenicity. Thus, the spleen cell population participating in the process of LPS-induced CSF generation is probably a nondividing, terminally differentiated one without need for DNA synthesis. In addition, it was also shown that active RNA and protein synthesis are needed in this process.
Animals↗
Effects of aging on granulopoietic activity (colony-stimulating factor).
This investigation was undertaken to determine whether there is a decrease of granulopoietic activity in subjects of the geriatric age group. Colony-stimulating factor (CSF) is an alpha glycoprotein which causes proliferation of granulocytes in vitro. A study was made of the variation in the level of CSF with age and the state of health in 78 subjects. They were classified into two groups-young (ages 22-60) and old (ages 70-94). The state of health was classified as normal, acute disease, or chronic disease. The results showed that serum CSF does vary with age and health. The CSF levels were higher in the young than in the old. For both age groups, the CSF levels were elevated in acute disease, and subnormal in chronic disease.
Acute Disease↗
A modified assay for studies of cultured granulocyte precursors: cryopreservation of stimulating mononuclear cells.
Mononuclear cells (MNC), isolated from peripheral blood of healthy donors, were cryoprotected by dimethyl sulfoxide and stored in liquid nitrogen. Colony-stimulating factor (CSF), produced by cryopreserved MNC, was compared with that of nonfrozen controls in a double-layer agar system with human bone marrow as target cells. Our results indicate that cryopreserved MNC retain their ability to stimulate myelopoiesis-committed stem cells after freezing. In addition, evidence was obtained that CSF of feeder layers changes, depending on the duration of preincubation and cell concentration. In a system where either stimulating or target cells are cryopreserved the dynamics of interactions between normal or abnormal cell lines can thus be studied.
Blood Preservation↗
Granulopoiesis in cultures in human haemopoietic cells.
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Bone Marrow↗
Fractionation of antibodies to L-cell colony-stimulating factor by affinity chromatography.
Purified L-cell colony-stimulating factor (CSF) was coupled to cyanogen-bromide-activated Sepharose and used to selectively fractionate antibodies to this factor. With the use of a simplified two-step washing and elution technique, there was 50%--70% binding of the anti-CSF, with recovery of 60%--100% of the bound material. Both the native antiserum and purified anti-CSF fractions were inhibitory to murine granulocyte-macrophage colony formation. The purified antibodies contained only IgG and were reduced in protein concentration to 0.1% of the serum IgG values. These fractions should prove useful tools for the study of granulocyte and macrophage differentiation.
Animals↗
The exceptional responsiveness of certain human myeloid leukemia cells to colony-stimulating activity.
We have studied the marrow cells from a patient with acute myeloid leukemia (AML) for their responsiveness to colony-stimulating activity (CSA) in vitro. The AML cells were stimulated by CSA to rapid and extended growth in liquid culture. In the absence of CSA, the majority of cells died. CSA also stimulated the clonal growth of AML cells, and the minimum requirement for CSA was one-tenth to one-fiftieth that required to stimulate the growth of normal marrow CFU-C. CSA for AML cells was eluted from Sephacryl S-200 columns in fractions that represented an apparent molecular weight of 45,000 daltons. This fraction also produced optimal stimulation of normal human marrow. During remission, the patient's marrow cells did not grow in liquid culture and produced normal numbers of granulocytic and erythroid colonies in response to CSA and erythropoietin. Extended culture of the AML cells resulted in cell differentiation evidenced by decreasing proliferative capacity and by morphological and histochemical changes. These studies indicate that certain AML cells are extraordinarily responsive to CSA, an in vitro mediator of normal granulopoiesis.
Adult↗
Immunologic functions and in vitro activation of cultured macrophage tumor lines.
Five murine monocyte of macrophage tumor lines adapted to culture were characterized for differentiated properties. They ingested zymosan and latex beads, bore receptors for immunoglobulin and complement, synthesized lysozyme (most of which was secreted), and produced granulocyte colony-stimulating activity, either spontaneously or inducibly. Some of the lines also mediated phagocytosis and exocytosis of red blood cells (RBC) and lysis of tumor targets, dependent on the presence of specific antitarget sera. All the lines were growth inhibited by zymosan and Mycobacterium bovis BCG, but not by latex beads. Other macrophage-activating agents, dextran sulfate and lipopolysaccharide (LPS), as well as tuberculin purified protein derivative (PPD), inhibited most of the lines. Except for Fc and C receptors, most of the above properties were not found with other types of hematopoietic tumors in culture. In attempts to activate the macrophage lines in vitro to the "angry" state, we found that preincubation with concentrations of LPS and PPD cytostatic to the cells stimulated antibody-dependent RBC lysis, but not antibody-independent or tumor cytolysis. A classification of monocyte-related tumors and normal cells is proposed based on functional activities and differential sensitivity to immunostimulating agents.
Animals↗
Co-regulation of type C RNA virus production and cell differentiation in myeloid leukemic cells.
Mouse myeloid leukemic cells which differ in their competence to be induced to differentiate by the normal macrophage- and granulocyte-inducing protein MGI have been used to study the relationship between type C RNA virus production and myeloid cell differentiation. Clones which can be induced by MGI to form Fc and C3 rosettes, to synthesize and secrete lysozyme and to differentiate to mature macrophages and granulocytes (MGI+D+) were induced by MGI to produce higher amounts of type C virus. Clones (MGI+D-) that were less inducible by MGI for Fc and C3 rosettes and lysozyme and were not induced to from mature cells were also less inducible higher virus production. In both types of clones, the increased virus production induced by MGI preceded the induction of rosettes and lysozyme. Clones that were not induced by MGI for rosettes or lysozyme (MGI-D-) showed little or no enhancement of virus production. MGI did not affect virus production in erythroleukemic cells, and erythropoietin did not affect virus production in the myeloid leukemic cells. Dexamethasone, lipopolysaccharide, dimethylsulfoxide and low concentrations of actinomycin D can induce some differentiation-associated properties in some of the clones. With these compounds, there was also a direct relationship between the enhancement of virus production and induction of differentiation-associated properties. Virus released from the three types of clones before or after treatment with MGI or dexamethasone was identified as N-tropic. The enhancement of virus production, as measured by reverse transcriptase activity, was accompanied by an increase in the amount of the viral protein p30, and interferon, which idd not inhibit the induction of differentiation in the myeloid leukemic cells, also did not prevent the increase in the amount of p30. After the early enhancement of virus production associated with the induction of differentiation, a shut-off of virus production occurred in the mature cells induced by MGI in MGI+D+ clones, whereas clones that did not differentiate to mature cells continued to produce virus. The results indicate that enhancement of virus production appears to be an early step in the induction of differentiation. Once induction has occurred, the lack of virus production in the mature cells suggest that a subsequent shut-off of virus production may be required for the completion of differentiation to mature cells. This relationship between cell differentiation and virus production suggests that type C virus has a regulatory role in myeloid cell differentiation.
Animals↗
Cellular responsiveness to stimulation in vitro: increased responsiveness to colony stimulating factor of bone marrow colony-forming cells treated with surface-active agents and cyclic 3'5' AMP.
Addition of low concentrations (10 ng/ml) of saponin or Tween 80 to stimulated cultures of normal mouse bone marrow in agar increased the number of granulocyte-macrophage colonies which developed. Addition of cyclic AMP or dibutyryl cyclic AMP in low concentration (10(-8) to 10(-10) M) also enhanced colony numbers although concentrations above 10(-5) M were inhibitory. enhancement was found when marrow cells were pre-treated with these agents and cultured in their absence. The agents did not stimulate colony development in the absence of colony-stimulating factor and enhancement of colony number occurred only in cultures containing a concentration of colony-stimulating factor which was sub-optimal in terms of maximum colony development. There was no indication of increased colony-stimulating factor production by treated marrow cells under the experimental conditions used to show colony enhancement. It was concluded that the agents caused an increased responsiveness of colony-forming cells to colony-stimulating factor.
Adenosine Monophosphate↗
Control of CFUc proliferation by selective endogenous inhibitors.
The susceptibility of mouse bone marrow colony forming cells (CFUc) to three different types of proliferation inhibitors in capillary semisolid agar gel was studied. GI-3, a target specific peptide containing granulocyte fraction, T4-1, an oligospecific thymic factor of proteid nature, and the alkylating cytostatics dianhydrogalactitol (DAD) inhibit myeloid colony formation as a function of concentration. The respective MED values amount to 8, 10, and 0.002 microgram/ml. When compared with this same parameter 3H-TdR incorporation into DNA of liquid bone marrow cultures showed a single fold charge for the endogenous inhibitors (GI-3, T4-1) for the cytostatic (DAD) a 3 to 4 fold lower difference. It was demonstrated, that in competitive antagonism of GI-3 and colony stimulating factor the inhibitor prevails over CSF.
Animals↗
The isolation and characterization of a colony stimulating factor from human lung.
Serum-free conditioned medium from human lung obtained at autopsy provides a rich source of colony stimulating factor which stimulates granulocytic and macrophagic colony growth in both mouse and human bone marrow. The appearance of the factor is enhanced by endotoxin and inhibited by either puromycin or actinomycin D. Human lung colony stimulating factor is stable at the pH range of 6.5-10 and temperature of 56 degrees C for 30 min. It is resistant to trypsin and neuraminidase but is sensitive to subtilisin, chymotrypsin and periodate. It shows heterogeneity on Sephadex gel filtration with two activity peaks having molecular weight of 200 000 and 40 000, respectively. Upon gel electrophoresis, human lung colony stimulating factor migrates in the alpha-globulin post-albumin region. Using the combination procedures of hydroxyapatite chromatography and preparative polyacrylamide gel electrophoresis a 600-fold purification was achieved with a final specific activity of 6-10(5) units per mg protein. The purified colony stimulating factor is very labile; however, the activity can be stabilized by the addition of gelatin or bovine serum albumin at the concentration of 0.1% and 0.2 mg/ml, respectively.
Chromatography↗
Virus susceptibility of mouse hemopoietic cells in vitro: inhibition of granulocyte-macrophage precursor cells by Newcastle disease virus.
Normal mouse bone marrow cells were exposed to encephalomyocarditis virus (EMC), reovirus type 3 (REO3), influenza virus (FLU), and Newcastle disease virus (NDV) then assayed for granulocyte-macrophage precursor cells by the technique of colony formation in agar. Exposure to EMC, REO3, and FLU caused a slight but variable loss of colony-forming potential, whereas exposure to NDV caused a very marked loss. NDV acted directly on the cells, not indirectly through release of colony-inhibiting factors or destruction of colony-stimulating factor. Experiments with NDV inactivated by heat, ether, or ultraviolet irradiation indicated that colony inhibition was associated with fully infective virus, even though some of the inactivated preparations had retained full hemagglutinin, neuraminidase, or hemolytic activity.
Animals↗
Functional and morphologic characterization of human T cells continuously grown in vitro.
Long-term growth (now over 13 months) of thymus-derived lymphocytes from numerous normal human bone marrow and peripheral blood cell samples was accomplished by using a factor present in media obtained from mitogen-stimulated human peripheral blood lymphocytes. This long-term growth could neither be initiated nor maintained by mitogens alone. All cell cultures were greater than 90% E rosette-positive, whereas the tests for B cell markers, surface IgG and IgM, and EAC rosette were routinely negative. There was no evidence for the presence of granulocytes, monocytes, and their precursors in these cultures. The E rosette-positive cells were then tested to see if they had T cell functions. PHA, Con A, and pokeweed mitogens stimulated lymphproliferative responses in these cultures comparable to those of fresh peripheral blood cells. These proliferating cells were also able to release cell mediators, such as interferon and colony-stimulating activity. Further evidence for the T lymphocyte nature of these cultured cells was obtained from one-way mixed leukocyte cultures in which these cells responded to but were unable to stimulate allogeneic cells. The functional and morphologic characteristics of these cultured cells show that these cells are T cells that grow continuously in vitro.
Cells, Cultured↗
Stimulation and inhibition of granulocyte and mononuclear colony formation in vitro by conditioned medium from mouse peritoneal cells.
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Animals↗
Macrophage colony development: properties of colony stimulating factors from murine embryo and pregnant uterus.
Extracts from embryonic and uterine tissue of mice, operationally defined as colony stimulating factor (CSF), promoted the growth of macrophage-granulocyte colonies in vitro. Uterine CSF focusses from pH 5.15 to 6.00 and embryonic CSF from pH 3.60 to 5.20, although both forms have similar biological activity. CSF is relatively resistant to denaturation but it is inactivated by periodate and dithiothreitol. Gel filtration indicates a molecular weight of 45,000 which is unchanged following treatment with insolubilized trypsin, a procedure which affords a useful purification (240-fold). Trypsin-sensitive material in CSF preparations modifies colonial form under certain conditions of culture, probably by increasing the motility of macrophages. Diaminoethane derivatives of CSF were prepared and retained biological activity at isoelectric points above pH 9.0. These derivatives may be covalently linked to Sepharose providing an insolubilized form of CSF to study interactions of CSF with the cell surface.
Animals↗