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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 this report a method for the affinity purification and radiolabeling of recombinant mouse interleukin (IL)-4 is described. It is shown on the basis of several criteria that IL-4 retains full biologic activity after radioiodination and can therefore be used as a valid model for measuring the binding characteristics of native IL-4. By using Scatchard plot analysis of equilibrium binding data, it is demonstrated that 125I-IL-4 binds to a high affinity cell surface receptor which is expressed by both hemopoietic and nonhemopoietic cells. The dissociation constant for 125I-IL-4 (Kd = 20 to 60 pM) corresponds to the concentration of IL-4 which gives 50% biologic activity (i.e., 10 to 30 pM). Binding of 125I-IL-4 is rapid (t1/2 of 2 min), whereas dissociation occurs at a slow rate (t1/2 approximately 4 hr). The IL-4 receptor shows a high degree of specificity. Whereas unlabeled mouse IL-4 competed with mouse 125I-IL-4 in an equimolar fashion for binding to IL-4 receptors, several other lymphokines, including mouse IL-2, IL-3, interferon-gamma, granulocyte-macrophage colony-stimulating factor, and human IL-1, IL-2, and IL-4 were unable to inhibit, even at molar excesses of 400 to 800-fold. At 37 degrees C, 125I-IL-4 is rapidly internalized (approximately 200 molecules/cell/min) by HT-2 cells, with at least 85% of cell surface receptors being functional in this respect. Receptors for IL-4 were found to be expressed by subclasses of T and B cells, mast cells, macrophages, and by cells of the myeloid and erythroid lineages. This wide distribution of receptor expression closely matches the known spectrum of biologic activities of IL-4, including proliferation and/or differentiation of T and B cells, mast cells and granulocytes, and induction of macrophage antigen-presenting capacity. IL-4 receptors were also found on a variety of nonhemopoietic cells such as cloned stromal cell lines from the bone marrow, spleen, thymus, and brain, and on muscle, brain, melanoma, fibroblast, and liver cells. Indeed, only 5 of more than 90 cell types tested have undetectable numbers of IL-4 receptors. The biologic effects of IL-4 on nonhemopoietic cells have not yet been reported and await elucidation.
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PMID:Expression of high affinity receptors for murine interleukin 4 (BSF-1) on hemopoietic and nonhemopoietic cells. 296 13

Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) is a powerful growth and differentiation factor which acts on hematopoietic progenitor cells and also activates differentiated granulocytes and macrophages. This study shows that mouse peritoneal macrophages can be induced to accumulate GM-CSF mRNA and to release GM-CSF by inflammatory agents (lipopolysaccharide, fetal calf serum, thioglycolate broth); phagocytosis; and adherence in the presence of fibronectin. GM-CSF mRNA accumulation, which is totally prevented by the corticosteroid dexamethasone and by interferon-gamma, is not accompanied by changes in the gene's transcriptional level. No interleukin 3 (multi-CSF) mRNA is detectable in induced macrophages. These findings have implications in the understanding of hematopoiesis and of the inflammation and repair process.
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PMID:Phagocytosis and inflammatory stimuli induce GM-CSF mRNA in macrophages through posttranscriptional regulation. 310 73

Colony-stimulating factor-induced bone marrow (BM) cultures are a good source of antigen-presenting macrophages. However, they failed to present antigen to T cell clones when antigen was introduced as a short pulse only. Adding interleukin 1 (IL1) to BM culture cells before antigen pulse restored their antigen-presenting activity concomitant to a 2-10-fold increase in Ia antigenicity. We performed a series of experiments to test the mechanism of this IL1-induced activation. Our findings suggest that IL1 influences Ia expression and antigen-specific T cell proliferation by inducing interferon-gamma (IFN-gamma) production. IFN-gamma is produced in this system probably by residual Thy-1-positive cells in the BM cell culture.
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PMID:Induction of interferon-gamma production and Ia expression by interleukin 1 in bone marrow culture cells. 310 62

The effects of recombinant human tumor necrosis factor (TNF), lymphotoxin (LT), and interferon-gamma (IFN-gamma) on the growth of human hemopoietic progenitor cells in clonal culture have been examined. Colony growth was induced by using granulocyte colony-stimulating factor (G-CSF), or granulocyte-macrophage colony-stimulating factor (GM-CSF). A suppressive effect of TNF, LT, and IFN-gamma on the development of granulocyte, macrophage, and mixed granulocyte/macrophage colonies was shown. Suppression of colonies formed after stimulation with G-CSF was greater than that observed after stimulation with GM-CSF. In the presence of a monoclonal antibody to TNF, or polyclonal antibodies to either LT or IFN-gamma, the inhibitory effect of the molecule to which the antibody was directed was abrogated. These findings suggest that progenitor cells responsive to G-CSF or GM-CSF have different sensitivities to the effects of TNF, LT, and IFN-gamma. Defining the interactions of growth factors and inhibitors should increase understanding of mechanisms underlying diseases associated with suppression of normal hemopoiesis, and in predicting the effects in vivo of these bioregulatory molecules in clinical medicine.
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PMID:The differential inhibition of hemopoietic growth factor activity by cytotoxins and interferon-gamma. 311 24

In this study microglial cells isolated from brain cell cultures of newborn mice were characterized and investigated for morphology, their responses to growth factors and their functional properties. The microglial cells were phagocytic, contained nonspecific esterase activity and expressed Fc (IgG1/2b) and type-3 complement receptors. Scanning electron microscopy revealed that in analogy to brain tissue two types of microglial cells are present in the cultures: the ameboid and the ramified type which both display similar appearance by transmission electron microscopy. Interleukin 3 and the granulocyte-macrophage colony-stimulating factor were potent growth factors for the cultured microglial cells. The cells were negative for class II antigens (Ia) of the major histocompatibility antigen complex. However, upon treatment with interferon-gamma (IFN-gamma) microglial cells became Ia+ and functioned as antigen-presenting cells when tested on ovalbumin-specific Ia-restricted helper T cells. Furthermore, microglial cells exposed to IFN-gamma and endotoxin developed tumor cell cytotoxicity and produced tumor necrosis factor alpha. Taken together, microglial cells share the characteristics of cells of the macrophage lineage.
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PMID:Antigen presentation and tumor cytotoxicity by interferon-gamma-treated microglial cells. 311 91

In order to investigate differences in control mechanisms between embryonic and adult hemopoiesis, we have studied the sensitivity of human embryonic progenitors (5-8 weeks postconception) to either positive (erythropoietin (Ep), granulocyte-macrophage colony-stimulating factor (GM-CSF) and insulin-like growth factor 1 (IGF-1] or negative (tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma] in vitro regulators of adult hemopoietic differentiation. Growth stimulators were analyzed under serum-deprived conditions whereas growth inhibitors were investigated in serum-supplemented culture. Formation of granulocyte-macrophage colonies from embryonic progenitors was induced by GM-CSF but inhibited by TNF and IFN-gamma. Early erythroid progenitors resemble adult erythroid burst-forming cells (BFU-E) in their sensitivity to Ep and TNF but differ in their lack of response to GM-CSF or other adult sources of burst-promoting activity, and absence of inhibition by IFN-gamma. IGF-1 promoted erythroid burst formation in the absence of insulin, but did not have Ep-like activity. These data indicate that embryonic and adult erythroid progenitors differ at least in terms of in vitro sensitivity to GM-CSF and IFN-gamma and suggest that different cellular response to control signals may underlie the differences observed in vivo between embryonic and adult hemopoiesis.
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PMID:Human embryonic hemopoiesis: control mechanisms underlying progenitor differentiation in vitro. 311 98

Regulation of the production of the biologically active vitamin D3 sterol 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] by cultured pulmonary alveolar macrophages (PAM) obtained from 6 patients with pulmonary sarcoidosis and from 9 normal subjects was studied. The sarcoid cells, all collected from patients with normal calcium metabolism, synthesized 1,25-(OH)2-[3H]D3 from the substrate 25-hydroxyvitamin [3H]D3 (25OH-[3H]D3), whereas in vitro incubation with recombinant human interferon-gamma (IFN gamma) or lipopolysaccharide (LPS) was required for induction of synthesis of the hormone by normal PAM. Exogenous 1,25-(OH)2D3 (10-100 nmol/L) decreased endogenous hormone production by normal PAM by approximately 45%. The relative inhibitory effect of 1,25-(OH)2D3 was less pronounced in sarcoid PAM, in which 10-100 nmol/L 1,25-(OH)2D3 inhibited 250HD3-1-hydroxylase by approximately 25%. An accompanying induction of the 250HD3-24-hydroxylase, which is typical for renal cells, was found at low levels in only 3 of 10 experiments; in this regard, no differences between sarcoid and normal PAM were apparent. PTH or forskolin did not influence 250HD3 metabolism by PAM. 1,25-(OH)2D3 production by sarcoid PAM was enhanced by lipopolysaccharide and IFN gamma. Likewise, recombinant human interleukin-2 stimulated 1,25-(OH)2D3 production by sarcoid PAM, suggesting a possible role for both IFN gamma and interleukin-2 in the induction of 1,25-(OH)2D3 synthesis by sarcoid PAM in vivo. Recombinant human IFN alpha, IFN beta, and granulocyte-macrophage colony-stimulating factor had little effect. Dexamethasone and chloroquine, which have in vivo antihypercalcemic activity in sarcoidosis, both inhibited 1,25-(OH)2D3 synthesis by sarcoid PAM; chloroquine simultaneously stimulated the 24-hydroxylase. Our studies suggest that the 250HD3-metabolizing system in PAM is in some respects different from renal metabolism of 250HD3.
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PMID:Regulation of 1,25-dihydroxyvitamin D3 production by cultured alveolar macrophages from normal human donors and from patients with pulmonary sarcoidosis. 311 53

Bone marrow-derived cells from C3H/HeJ mice were cultured in the presence of recombinant murine granulocyte-macrophage colony-stimulating factor (rGM-CSF) or highly purified murine macrophage colony-stimulating factor (CSF-1) for 7 days. Following this 7-day culture period, mature macrophages were harvested and replated at precise densities in the absence of exogenous rGM-CSF or CSF-1, and assayed in a two-signal tumoricidal assay. Cultures were stimulated with medium only or with combinations of recombinant interferon-gamma (rIFN-gamma) as the "priming" signal, and/or butanol-extracted lipopolysaccharide (But-LPS) as the "triggering" signal for 24 hr. At this time, 51Cr-labeled, P815 tumor target cells were added, and the percent tumor cell cytotoxicity was determined after 16 hr. Macrophages derived under the influence of rGM-CSF exhibited significant tumoricidal capacity with medium alone (16 +/- 5%). The addition of "priming" signal only (i.e., rIFN-gamma, 10.0 U/ml) significantly increased tumoricidal capacity to 31 +/- 9%. Treatment with But-LPS alone did not alter the basal tumoricidal activity of rGM-CSF-derived macrophages. Combinations of rIFN-gamma (10.0 U/ml) and But-LPS (0.5-5.0 micrograms/ml) generated highly tumoricidal macrophages (50-60% tumor cell cytotoxicity). In contrast, medium-treated CSF-1-derived macrophages exhibited a significantly lower basal level of tumor cytotoxicity (6 +/- 3%). Unlike rGM-CSF-derived macrophages, treatment of CSF-1-derived macrophages with high concentrations of rIFN-gamma alone did not increase significantly the level of cytotoxicity above that of medium-treated cultures. However, CSF-1-derived macrophages responded to the highest concentrations of But-LPS (5.0 micrograms/ml) to increase tumoricidal activity from 6 +/- 3% to 17 +/- 5%. Optimal tumoricidal activity (44 +/- 17%) was observed when CSF-1-derived macrophages were treated simultaneously with high concentrations of both rIFN-gamma and But-LPS. Thus, macrophages derived from bone marrow progenitors in either rGM-CSF or CSF-1 exhibited tumoricidal capacities that differed in basal activity as well as in their requirements for and sensitivities to "priming" and "triggering" signals.
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PMID:Bone marrow progenitors cultured in the presence of granulocyte-macrophage colony-stimulating factor versus macrophage colony-stimulating factor differentiate into macrophages with distinct tumoricidal capacities. 313 73

Recent studies have examined the synergistic effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and hematopoietin-1 (now identified as Interleukin-1, IL-1) on bone marrow colony formation. In the present report, human peripheral blood mononuclear cells (MNCs) were stimulated in vitro with recombinant human GM-CSF (rGM-CSF) and production of IL-1 alpha, IL-1 beta, and tumor necrosis factor (TNF) was measured by specific radioimmunoassays. In the MNCs of 20 individuals, rGM-CSF's ability to induce the three cytokines was variable. Nearly all donors responded to low-dose rGM-CSF (0.02 to 2 ng/mL) with production of TNF, whereas some individuals did not produce IL-1 alpha or IL-1 beta. The MNCs from some subjects stimulated with high-dose rGM-CSF (10 to 80 ng/mL) produced as much cytokine as in response to 10 ng/mL endotoxin. Localization (ie, extracellular or cell-associated cytokine) was specific for the cytokine rather than the stimulus. Indomethacin increased the amount of cytokine produced in response to rGM-CSF for IL-1 beta and TNF but not for IL-1 alpha. In addition, interferon-gamma (INF-gamma) upregulated the amount of TNF induced by rGM-CSF in all donors examined, with variable effect on IL-1 alpha and IL-1 beta. Suboptimal levels of endotoxin incubated with rGM-CSF did not alter the amount of IL-1 produced as compared with cells stimulated with rGM-CSF alone, whereas TNF production showed either no change or a slight decrease in production. These data suggest that GM-CSF may play an important role in the host defense response by stimulating production of these cytokines.
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PMID:Production of interleukin-1 alpha, interleukin-1 beta and tumor necrosis factor by human mononuclear cells stimulated with granulocyte-macrophage colony-stimulating factor. 197 Apr 88

Murine spleen and lymph node L3T4+ T cells were found to spontaneously produce high levels of interleukin 3 (IL3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in cultures containing 10% fetal calf serum (FCS) in the absence of other stimulation. The IL3 and GM-CSF activities in culture supernatants peake between the fifth and seventh day of culture. The specificity of the bioassays was attested by the use of rabbit anti-IL3 and anti-GM-CSF antibodies, as well as by the detection of a maximal accumulation of IL3 and GM-CSF mRNA on the fourth day. In contrast, no significant activities of IL2, IL4 or interferon-gamma were detected in these culture supernatants. The markedly limited production of IL3 and GM-CSF in cultures performed in 1% autologous normal mouse serum and the inhibitory effect of anti-Ia or anti-L3T4 monoclonal antibody strongly suggest that the selective production of most, if not all IL3 and GM-CSF by L3T4+ T cells is a result of activation of L3T4+ T cells by fetal calf serum. All the strains of mice tested except athymic nude mice produced substantial amounts of IL3 and GM-CSF during the culture. This is in contrast to a previous report (Palacios, Eur. J. Immunol. 1984. 14: 599), indicating that only spleen cells of the MRL strain homozygous for the lpr gene spontaneously release IL3 in cultures. We found that spleen and lymph node cells from MRL/MpJ-lpr/lpr or C57BL/6J-lpr/lpr mice released, in fact, much less IL3 and GM-CSF in cultures. This was, however, due to the high proportion of the peculiar lpr Ly-2-/L3T4-T cells in spleen and lymph nodes, since after depletion of this lpr T cell subset, lymph node cells from C57BL/6J-lpr/lpr mice produced IL3 and GM-CSF at levels comparable to those in C57BL/6J-+/+ mice. These results further support the notion that the lpr Ly-2-/L3T4- T cell subset is immunologically nonfunctional and its accumulation dilutes functional L3T4+ T cells in mice bearing the lpr mutation.
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PMID:Selective production of interleukin 3 (IL3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in vitro by murine L3T4+ T cells: lack of spontaneous IL3 and GM-CSF production by Ly-2-/L3T4- lpr subset. 313 30


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