Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a 23-kDa glycoprotein with remarkably diverse effects on immune and nonimmune cells. GM-CSF induces differentiation of granulocyte, macrophage, and eosinophil precursor cells. Proliferation of monocyte-macrophages, T lymphocytes, keratinocytes, and endothelial cells is also stimulated by GM-CSF. In addition, GM-CSF alters the functional properties of mature granulocytes, macrophages, eosinophils, and basophils. GM-CSF is produced by T lymphocytes, macrophages, and several cell types in extramedullary sites, where it may act in a paracrine manner to regulate the local response to antigenic challenge. Clinical trials of GM-CSF have been conducted in patients with AIDS, aplastic anemia, myelodysplastic syndromes, and sarcoma and following bone marrow transplantation and accidental radiation exposure. GM-CSF significantly increased circulating numbers of several myeloid cells and produced dose-dependent toxicity consisting primarily of myalgias, fever, fluid retention, and serosal effusions. Additional studies are needed to define the role of GM-CSF in treatment of patients with qualitative and quantitative dysfunction of immune cells.
...
PMID:Granulocyte-macrophage colony-stimulating factor: pleiotropic cytokine with potential clinical usefulness. 240 68

CD28 is a 44-kDa glycoprotein expressed as a homodimer on the surface of a major subset of human T cells. Previous studies have demonstrated that the binding of monoclonal antibodies to the CD28 surface antigen can augment the proliferation of purified human T cells stimulated with suboptimal doses of mitogens or anti-T-cell receptor/CD3 complex antibodies. In this report, we show that CD28 stimulation augments T-cell immune responses by specifically inducing a 5- to 50-fold enhancement in the expression and secretion of interleukin 2, tumor necrosis factor type alpha, lymphotoxin, interferon gamma, and granulocyte-macrophage colony-stimulating factor in normal human T cells stimulated to proliferate by crosslinking of the T-cell receptor/CD3 complex. This CD28-mediated induction of lymphokine/cytokine gene expression occurred even in T cells stimulated with optimal concentrations of mitogens or anti-T-cell receptor/CD3 antibodies, although under these conditions CD28 activation failed to enhance the proliferative response. The activation pathway induced by stimulation of CD28 is distinct from other biochemical pathways that induce lymphokines/cytokines because CD28 stimulation can induce lymphokine/cytokine gene expression in the presence of the immunosuppressant cyclosporine. Together these data suggest that the CD28 cell surface molecule is part of a distinct activation pathway that specifically modulates the expression of multiple lymphokine/cytokine genes.
...
PMID:CD28 activation pathway regulates the production of multiple T-cell-derived lymphokines/cytokines. 246 50

Five glycoprotein growth factors capable of stimulating the proliferation and differentiation of haemopoietic progenitor cells in vitro have been identified and sequenced over the past ten years. Recombinant DNA technology has recently enabled the production of sufficient amounts of these agents for preclinical testing. Erythropoietin (EPO), granulocyte-macrophage colony-stimulating factor (GM-CSF), and granulocyte colony-stimulating factor (G-CSF) have already entered clinical studies in humans. Interleukin-3 (IL-3) and macrophage colony-stimulating factor (M-CSF) should soon be available for use in humans. EPO corrects the anaemia of end stage renal failure, improving the quality of life for such patients and preventing the need for red cell transfusions. At high dose it increases platelet production in vitro and in vivo and may be of value in humans to prevent the thrombocytopaenia associated with chemotherapy. G-CSF and GM-CSF have been used in several clinical studies. Administration of both growth factors results in a leucocytosis, G-CSF predominantly increasing neutrophil production and GM-CSF increasing production of neutrophils, eosinophils and monocytes. The optimal administration of these agents is via continuous intravenous infusion or daily subcutaneous injections at doses of 3-10 micrograms/kg/24 h. GM-CSF has shown promising results in patients with AIDS and the myelodysplastic syndrome and both G-CSF and GM-CSF have reduced the duration of neutropaenia and incidence of infection associated with chemotherapy. These agents may allow an escalation of the dose-intensity of chemotherapy in the future and thereby, hopefully, increase the response rate and survival for patients with a variety of neoplasms. Several other potential roles for these haemopoietic growth factors are discussed.
...
PMID:Clinical trials with haemopoietic growth factors. 249 Dec 51

Leukemia inhibitory factor (LIF) is a glycoprotein regulator that induces the differentiation and suppresses the clonogenicity of M1 myeloid leukemic cells. M1 cells require only a brief exposure to LIF to become irreversibly committed to differentiation. In combination with granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor, LIF is also able to suppress HL-60 and U937 cell proliferation. Normal monocytes and macrophages have LIF receptors, but the function of LIF on such cells is unclear. Recently it was discovered that LIF also acts on embryonic stem (ES) cells, where its continuous presence is required to prevent ES cell differentiation.
...
PMID:The pleiotropic actions of leukemia inhibitory factor. 251 84

The ability of malignant cells to respond to growth factor(s) present in or secreted by a distant target organ may be important in tumor metastasis. We used metastatic cell lines and clones of the rat 13762NF mammary adenocarcinoma that show reproducible spontaneous metastatic behavior from the mammary fat pad to regional lymph nodes and lung sites. Whereas poorly lung metastatic MTPa and MTC cells did not grow in response to lung-conditioned medium, highly lung-metastatic MTLn3 cells responded and grew rapidly in lung-conditioned medium. The major growth-promoting factor for MTLn3 cells from porcine and rat lung-conditioned media was purified by using hydroxylapatite affinity and anion exchange chromatography, chromatofocusing, size exclusion chromatography, and preparative native gel electrophoresis. The activity in each of the purification fractions was measured by determining their ability to increase the number of MTLn3 cells in serum-deprived culture. The major component that differentially stimulated the growth of highly metastatic MTLn3 cells was a glycoprotein of Mr approximately 66,000. Under reducing conditions, its apparent Mr was approximately 72,000. This lung-derived mitogen was stable at pH 4.0-9.0, possessed a pI of 6.9-7.0, and preferentially promoted the growth of lung-metastasizing tumor lines over their poorly lung-metastasizing counterparts in rat 13762NF mammary adenocarcinoma and murine B16 melanoma tumor systems. The activity of porcine lung-derived growth factor was not affected by pretreatment with antisera to porcine insulin, human granulocyte-macrophage colony-stimulating factor, human platelet-derived growth factor, or murine epidermal growth factor. It was inactivated by reduction with dithiothreitol or exposure to high temperature (95 degrees C). The results suggest that specific organ-derived growth factors are important in metastatic colonization and organ growth of particular malignant cells.
...
PMID:Purification and some properties of a lung-derived growth factor that differentially stimulates the growth of tumor cells metastatic to the lung. 254 64

Aplastic anemia serum (AAS) contains humoral factors that alter both proliferation and maturation of human megakaryocytes (MK). The ability of AAS to augment MK colony formation (colony-forming unit, CFU-MK) was neutralized by an antiserum against MK colony-stimulating factor (MK-CSF), a glycoprotein isolated from AAS. The adsorbed AAS still retained the ability to accelerate cytoplasmic maturation of recognizable MK. Similar experiments were done with thrombocytopoiesis-stimulating factor (TSF) and an anti-TSF antiserum to further define the activity in AAS responsible for accelerating cytoplasmic maturation. Bone marrow fractions enriched for recognizable human MK, but devoid of CFU-MK, were obtained by centrifugal elutriation and placed in short-term liquid cultures. MK progressed through identifiable maturation stages (1-4) more quickly in the presence of either TSF or AAS. TSF slightly enhanced the cloning efficiencies of CFU-MK, but did not alter the number of MK in individual colonies derived from non-adherent, low-density, T-cell-depleted bone marrow. In contrast, granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 3 (IL-3), and crude AAS substantially augmented both MK colony formation and cells per colony. TSF also doubled the percent 35S incorporation into platelets of immunothrombocythemic mice, but stimulation was completely abolished by anti-TSF. Anti-TSF antiserum was then used to analyze the promotion of MK colony formation by cytokines. Cloning efficiencies of CFU-MK were reduced to baseline values when TSF was pretreated with anti-TSF; however, the MK colony-stimulating activity (MK-CSA) of GM-CSF, IL-3, or AAS was not altered by adsorption with anti-TSF. In contrast, the cytoplasmic maturation of recognizable MK was slower, and fewer mature stage-4 cells were present at days 1-3 in AAS adsorbed with anti-TSF than MK cultured in AAS treated with normal rabbit serum or untreated AAS. Therefore, TSF appears to be a major factor in AAS that accelerates terminal maturation of human MK. TSF primarily affects megakaryocytopoiesis by promoting MK maturation rather than enhancing CFU-MK proliferation.
...
PMID:Effects of thrombocytopoiesis-stimulating factor on terminal cytoplasmic maturation of human megakaryocytes. 268 80

Erythropoiesis is regulated by the glycoprotein hormone erythropoietin (Epo) and by several other factors including interleukin 3 (IL-3) and granulocyte-macrophage colony-stimulating factor. The possibility that IL-3 and GM-CSF may act by modulating Epo receptor expression was investigated using erythroblasts purified from the spleens of phenylhydrazine-treated mice. AT 37 degrees C, in the presence of sodium azide to inhibit receptor internalization. 125I-labeled human recombinant Epo bound to a single class of high-affinity receptors on splenic erythroblasts (450 sites/cell, Kd = 700 pM). Autoradiographic studies indicated that 94% of specifically bound Epo was associated with erythroblasts, decreased Epo binding being observed with increasing erythroid cell maturation. Whereas recombinant mouse IL-3 and GM-CSF did not compete with 125I-Epo for binding to the Epo receptor, preincubation of cells with IL-3 resulted in a concentration-dependent loss of 125I-Epo binding without altering the affinity of residual receptors for Epo. Complete loss of Epo receptors was effected within 2 h at IL-3 concentrations above 2500 U/ml. Preincubation with recombinant mouse GM-CSF had no effect on binding, even at 100,000 U/ml. In comparison, preincubation of cells with Epo (50 U/ml) caused complete loss of 125I-Epo binding within 30-60 min, an effect not explained by receptor saturation with unlabeled Epo. Thus, in addition to trans-down-modulating growth factor receptors of the granulocyte-macrophage series, IL-3 also trans-down-modulates a growth factor receptor of the erythroid lineage.
...
PMID:Down-modulation of high-affinity receptors for erythropoietin on murine erythroblasts by interleukin 3. 284 74

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) is a 22,000-dalton glycoprotein that stimulates the growth of myeloid progenitor cells and acts directly on mature neutrophils. A full-length complementary DNA clone encoding human GM-CSF was used as a probe to screen a human genomic library and isolate the gene encoding human GM-CSF. The human GM-CSF gene is approximately 2.5 kilobase pairs in length with at least three intervening sequences. The GM-CSF gene was localized by somatic cell hybrid analysis and in situ hybridization to human chromosome region 5q21-5q32, which is involved in interstitial deletions in the 5q- syndrome and acute myelogenous leukemia. An established, human promyelocytic leukemia cell line, HL60, contains a rearranged, partially deleted GM-CSF allele and a candidate 5q- marker chromosome, indicating that the truncated GM-CSF allele may reside at the rejoining point for the interstitial deletion on the HL60 marker chromosome.
...
PMID:The human gene encoding GM-CSF is at 5q21-q32, the chromosome region deleted in the 5q- anomaly. 299 78

Colony-stimulating factor 1 (CSF-1) is a glycoprotein growth factor that specifically regulates the survival, proliferation and differentiation of mononuclear phagocytes and their precursors via a cell surface receptor selectively expressed on these cell types. The purified receptor is a single glycosylated polypeptide, Mr 165 000, which exhibits CSF-1-dependent autophosphorylation in tyrosine. CSF-1 alone regulates cells of the mononuclear phagocytic series (CSF-1-dependent colony-forming unit [CFU-C]----monoblast----promonocyte----monocyte----macrophage). However, the presence of a multipotent haemopoietic cell growth factor, haemopoietin-1, permits CSF-1 to stimulate precursors of CFU-C to proliferate and differentiate to macrophages. Precursors of CFU-C possess low levels of the CSF-1 receptor but there is an increase in receptor levels on CFU-C just before their differentiation to adherent, proliferating mononuclear phagocytes. As the timing of this developmentally associated increase in receptor expression coincides with the acquisition of responsiveness to CSF-1 alone, it is an early indicator of determination to the mononuclear phagocytic lineage.
...
PMID:Action of the colony-stimulating factor, CSF-1. 301 14

Colony-stimulating factor 1 (CSF-1) regulates the survival, proliferation, and differentiation of mononuclear phagocytes. The CSF-1 receptor was purified from cell membranes of the J774.2 mouse macrophage cell line by solubilization with Triton X-100, CSF-1 affinity chromatography, and gel filtration. The purified receptor is a protein or glycoprotein of 165 kDa comprising a single polypeptide chain that is not covalently associated, either as a homopolymer, or with any other protein. CSF-1 stimulated autophosphorylation of the purified receptor in tyrosine residues. Casein but not histone was shown to act as a substrate for the tyrosine protein kinase activity of purified receptor.
...
PMID:Purification of the colony-stimulating factor 1 receptor and demonstration of its tyrosine kinase activity. 302 75


<< Previous 1 2 3 4 5 6 7 8 Next >>

---