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)

The histamine-producing cell-stimulating factor (HCSF) was first described as a lymphokine which is produced during secondary mixed leukocyte culture and which induces increased histamine synthesis by murine hematopoietic cells. It has been shown that it is different from interleukin 3 (IL 3), despite the fact that pure IL 3 expresses HCSF activity. Our results provide evidence that this factor (constitutively produced by the P388 D1 cell line) is identical with granulocyte-macrophage colony-stimulating factor (GM-CSF) i.e.: (a) physiochemical properties of HCSF and GM-CSF, such as molecular weight, isoelectric charge, hydrophobicity and behavior during affinity chromatography, are indistinguishable and both activities coelute during all biochemical purification procedures; (b) increased bone marrow cell histamine synthesis induced by P388 D1-derived HCSF is inhibited by anti-GM-CSF antiserum; (c) the GM-CSF cDNA probe hybridizes with a poly(A)+RNA from P388 D1 cells while no hybridizing signal was obtained with poly(A)+RNA from WEHI-3 and from P815 cells. On the other hand, the IL 3 cDNA probe hybridizes with a 1.0-kb poly(A)+RNA from WEHI-3 but not with those from P388 D1 and P815. Moreover, well known sources of GM-CSF, such as lung conditioned medium and semi-purified GM-CSF from phytohemagglutinin-induced supernatant of the murine T lymphoma LBRM-33-5 A4 (preparation devoid of IL 3), as well as recombinant murine GM-CSF, induce increased histamine synthesis by hematopoietic cells. All these results demonstrate that, in our culture conditions, the P388 D1 cell line spontaneously produces GM-CSF which is responsible for the P388 D1-induced HCS activity. Consequently, the latter is a property shared by the two distinct hematopoietic growth factors acting on the less committed cells, i.e. IL 3 and GM-CSF, whereas M-CSF or G-CSF are unable to induce histamine production. Interestingly, IL-4 which is known to support established mast cell line proliferation cannot induce HCS activity. In addition, none of the other cytokines tested, such as IL 1, IL 2, interferons or tumor necrosis factor can express HCS activity. This expression seems to be a specific property of IL 3 and GM-CSF.
...
PMID:Histamine-producing cell-stimulating activity. A biological activity shared by interleukin 3 and granulocyte-macrophage colony-stimulating factor. 288 59

The hemopoietic growth factor granulocyte-macrophage colony-stimulating factor, GM-CSF, specifically controls the production of granulocytes and macrophages. This report describes the binding of biologically-active 125I-labeled murine GM-CSF to a range of hemopoietic cells. Specific binding was restricted to murine cells and neither rat nor human bone marrow cells appeared to have surface receptors for 125I-labeled GM-CSF. 125I-Labeled GM-CSF only appeared to bind specifically to cells in the myelomonocytic lineage. The binding of 125I-labeled GM-CSF to both bone marrow cells and WEHI-3B(D+) was rapid (50% maximum binding was attained within 5 min at both 20 degrees C and 37 degrees C). Unlabeled GM-CSF was the only polypeptide hormone which completely inhibited the binding of 125I-labeled GM-CSF to bone marrow cells, however, multi-CSF (also called IL-3) and G-CSF partially reduced the binding of 125I-labeled GM-CSF to bone marrow cells. Interestingly, the binding of 125I-labeled GM-CSF to a myelomonocytic cell line, WEHI-3B(D+), was inhibited by unlabeled GM-CSF but not by multi-CSF or G-CSF. Scatchard analysis of the binding of 125I-labeled GM-CSF to WEHI-3B(D+) cells, bone marrow cells and peritoneal neutrophils indicated that there were two classes of binding sites: one of high affinity (Kd1 = 20 pM) and one of low affinity (Kd2 = 0.8-1.2 nM). Multi-CSF only inhibited the binding of 125I-labeled GM-CSF to the high affinity receptor on bone marrow cells: this inhibition appeared to be a result of down regulation or modification of the GM-CSF receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Specific binding of radioiodinated granulocyte-macrophage colony-stimulating factor to hemopoietic cells. 299 Sep 15

The in vitro production of eosinophils from committed progenitor cells is influenced by interleukin (IL)-5 (eosinophil differentiation factor) and to a lesser extent by IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF). In primary suspension cultures of marrow cells taken from eosinophilic mice, IL-3 induced a modest stimulation of eosinophil production compared to IL-5. In contrast, IL-3 was sevenfold more effective than IL-5 in generating eosinophil progenitors (eosinophil colony-forming units (CFU-eo] from more primitive precursors present in the marrow of normal mice. Pre-incubation of marrow cells in suspension culture with IL-3, but not IL-5, increased the recovery of myeloid precursors responsive to G-CSF, GM-CSF, CSF-1, or IL-3 two- to fourfold while eosinophil progenitor cells responsive to IL-5 were increased by more than 70-fold. Similarly, pre-incubation of bone marrow cells under clonal conditions with IL-3, but not IL-5, resulted in a more than 50 fold increase in CFU-eo responsive to IL-5 over input values. Bone marrow from mice pre-treated with 5-fluorouracil is greatly depleted of progenitor cells directly responsive to IL-3 or IL-5. IL-1 which synergistically interacts with various CSF species to confer a clonogenic response by primitive stem cells present in 5-fluorouracil-treated marrow also failed to stimulate eosinophil production. A marked synergism was observed when IL-1 and IL-3 were combined in the suspension pre-culture phase with a more than sixfold recovery of CFU-eo than induced by either factor alone. Furthermore, pre-culture of 5-fluorouracil-treated marrow cells with a combination of IL-1 and IL-3 resulted in a more than 260-fold increase of CFU-eo over input numbers. These data suggest that the concatenate action of IL-1, IL-3, and IL-5 is an absolute requirement for the in vitro generation of eosinophils from primitive hemopoietic stem cells.
...
PMID:Synergism among interleukin 1, interleukin 3, and interleukin 5 in the production of eosinophils from primitive hemopoietic stem cells. 325 32

Interleukin-1 (IL-1), recently identified as hemopoietin-1, affects hematopoiesis by presumably direct and indirect mechanisms. IL-1 stimulates primitive hematopoietic stem cells to express receptors for the granulocyte-macrophage colony-stimulating factors (GM-CSFs) and stimulates CSF release from accessory cells. We used highly purified murine granulocyte-macrophage progenitor cells (CFU-GM, up to 92% cloning efficiency) to assess the effects of IL-1 alpha on the proliferation, differentiation, and survival of these cells. The results demonstrated that IL-1 alpha does not directly influence the proliferation or differentiation of purified CFU-GM in the presence of plateau concentrations of purified natural or recombinant CSFs, and IL-1 alpha lacks intrinsic CSF activity of its own. CSF deprivation studies showed that IL-1 alpha rapidly (within one hour) promoted CFU-GM survival in the absence of CSF. This enhanced survival stimulated by IL-1 alpha was observed with CFU-GM responding to purified recombinant GM-CSF, natural M-CSF, recombinant G-CSF, recombinant IL-3, or IL-3 in WEHI-conditioned medium, and no effect on the pattern of CFU-GM differentiation occurred in cultures incubated with IL-1 alpha in the absence of CSF. The IL-1 alpha effects on CFU-GM are probably due to a direct action on progenitor cells because the presence or absence of accessory cells did not alter the results and concentrations of the CSFs that were too low to stimulate the proliferation of CFU-GM could not mimic the IL-1 alpha effect on CFU-GM survival.
...
PMID:Interleukin-1 alpha enhances the in vitro survival of purified murine granulocyte-macrophage progenitor cells in the absence of colony-stimulating factors. 326 52

Colony-stimulating factors are required for survival proliferation, differentiation and functional activation of granulocytes, macrophages and their precursor cells. In the present report, however, we demonstrate antiproliferative activity of recombinant human (rh) granulocyte-macrophage colony-stimulating factor (GM-CSF) on monoblast cell line U-937 and provide evidence for the involvement of tumor necrosis factor alpha TNF-alpha and interleukin 1 beta (IL 1 beta) in its growth inhibitory action. GM-CSF (but not granulocyte CSF, G-CSF or macrophage CSF, M-CSF) suppressed DNA synthesis and self renewal of U-937 cells. Similarly, medium conditioned by U-937 cells in response to GM-CSF (GM-CSF U-937-CM) was able to reduce clonogenicity and [3H]thymidine uptake by U-937 cells. Since neutralization of GM-CSF present in GM-CSF U-937-CM by monoclonal antibody to GM-CSF did not abrogate the autoinhibitory activity present in GM-CSF U-937-CM, we considered the possibility that other soluble molecules are released by U-937 cells upon GM-CSF stimulation. Neutralization by antibodies to IL 1 beta and TNF-alpha suggested that both monokines could be the antiproliferative principle operating in GM-CSF U-937-CM. Moreover, employing IL 1 beta-specific enzyme-linked immunosorbent assay, TNF-alpha specific radioimmunoassay, Northern analysis using a cloned TNF-alpha-specific cDNA and an oligonucleotide probe for IL 1 beta, we demonstrate GM-CSF-inducible IL 1 beta and TNF-alpha gene expression by U-937 cells at the mRNA and protein level. Although M-CSF expression was induced under similar conditions, M-CSF failed to inhibit growth of U-937 cells.
...
PMID:Recombinant human granulocyte-macrophage colony-stimulating factor induces secretion of autoinhibitory monokines by U-937 cells. 328 50

The activities of four purified human growth factors: biosynthetic (recombinant) granulocyte-macrophage colony-stimulating factor (GM-CSF); recombinant erythroid-potentiating activity (EPA); natural and recombinant pluripoietin (Ppo); and natural pluripoietin alpha (Ppo alpha), were compared on the growth of hematopoietic colonies from enriched populations of human marrow and blood progenitor cells. Conditioned medium from the Mo T cell line (MoCM) was used as a standard positive control. We found that activities of GM-CSF and Ppo alpha on the growth of hematopoietic colonies were indistinguishable; Ppo alpha is now believed to be identical to GM-CSF. Both factors were able to promote the growth of colonies derived from subpopulations of CFU-GM, BFU-E, and CFU-GEM. Colonies derived from CFU-GM and CFU-GEM in cultures stimulated by GM-CSF and Ppo alpha were much smaller than in cultures stimulated by MoCM. In contrast to previous reports in which less highly enriched progenitors were used as target cells, Ppo had no detectable activity on the growth of colonies derived from BFU-E or CFU-GEM but promoted the growth of a subpopulation of CFU-GM derived colonies. Ppo is now recognized to be identical to G-CSF. The GM colonies in cultures stimulated by G-CSF (Ppo) were much smaller than in cultures stimulated by MoCM. EPA had no detectable activity on either the size or number of colonies derived from CFU-GM, BFU-E, or CFU-GEM. Results from experiments using target cell populations of marrow fractions separated by velocity sedimentation and marrow populations following freezing suggested that GM-CSF (Ppo alpha) and G-CSF (Ppo) primarily affect the growth of relatively mature subpopulations of progenitor cells. It is clear from these results that additional factor(s) are present in MoCM that are necessary to stimulate CFU-GM, BFU-E, and CFU-GEM maximally in vitro.
...
PMID:Activities of four purified growth factors on highly enriched human hematopoietic progenitor cells. 349 80

The control of haematopoietic colony-stimulating factors (CSF) gene expression by interleukin 1 (IL-1) and tumour necrosis factor alpha (TNF-alpha) in cultured endothelial cells was studied by RNA hybridization and nuclear gene transcription. Both IL-1 and TNF-alpha induced, with somewhat different kinetics, a slow but marked accumulation of granulocyte-macrophage (GM)- and granulocyte (G)-CSF mRNAs in endothelial cells; macrophage (M)-CSF mRNA increased more rapidly but more moderately. Simultaneous treatment with maximally stimulating concentrations of both IL-1 and TNF-alpha had an additive effect on the accumulation of the three mRNAs, suggesting that both mediators act via independent pathways. The mechanism of CSF mRNA accumulation in endothelial cells was explored by nuclear run-on experiments, which showed that both IL-1 and TNF-alpha increase GM-CSF, G-CSF and M-CSF gene transcription to varying degrees.
...
PMID:Additive effects of interleukin 1 and tumour necrosis factor-alpha on the accumulation of the three granulocyte and macrophage colony-stimulating factor mRNAs in human endothelial cells. 349 13

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) was purified from 3 liters of serum-free conditioned medium of the Hodgkin's tumor cell line L428 KSA. The conditioned medium contained a high specific activity of 2.5 X 10(5) units of total colony-stimulating factor per mg protein. Colony-stimulating factor activity was determined by colony formation by human fetal liver cells or mouse bone marrow cells. The latter bioassay discriminated colony-stimulating factor 1, a subclass specific for monocyte/macrophage production, and G-CSF, specific for granulopoiesis, from GM-CSF. The starting material contained predominantly GM-CSF with CSF-1 and G-CSF constituting 10% and 12%, respectively, of the total activity. A seven-stage purification scheme was employed. The first stage involved concentration by batch chromatography on calcium phosphate gel. Subsequent stages involved gel filtration on Ultrogel AcA44, affinity chromatography on concanavalin A-Sepharose, batch chromatography on calcium phosphate gel and high-performance liquid chromatography on C1 reversed-phase (TSK TMS-250), gel permeation and C8 reversed-phase columns. The purified material showed a single disperse band, having an Mr of 30,000, by silver staining on sodium dodecyl sulfate polyacrylamide gel electrophoresis. An amino-terminal sequence of 20 amino acids was determined in a gas-phase sequencer with 500 ng of purified material. The sequence was identical to that predicted from the cDNA sequence. It was active on human fetal liver cells with half-maximum colony formation at 1 X 10(-12) M, but was not active on mouse bone narrow cells.
...
PMID:Human granulocyte-macrophage colony-stimulating factor purified from a Hodgkin's tumor cell line. 353 1

The effect of interleukin 10 (IL-10) on proliferation and cytokine secretion by acute myelogenous leukemia (AML) blast cells was investigated in vitro. IL-10 inhibited spontaneous AML blast proliferation for a majority of patients, whereas in the presence of exogenous growth factors (granulocyte-stimulating factor, G-CSF; granulocyte-macrophage colony-stimulating factor, GM-CSF; interleukin 3) the IL-10 effect on blast proliferation showed a wide variation depending on the individual AML patient. IL-10 seemed to cause an irreversible inhibitory effect on AML blasts, as inhibition could also be demonstrated when IL-10 was present only during the initial preincubation of the leukemia cells. IL-10 also inhibited AML blast colony formation. However, independent of the effect on AML blast proliferation, IL-10 decrease cytokine secretion from AML blast cells for all patients, as demonstrated for IL-1 alpha, IL-1 beta, tumor necrosis factor-alpha, GM-CSF and interleukin 6. IL-10 did not inhibit development of apoptosis in AML blasts cultured in vitro. Expression of complement receptors and capability to adhere and internalize bacteria by AML blasts were not altered by IL-10.
...
PMID:Effects of interleukin 10 on blast cells derived from patients with acute myelogenous leukemia. 747 83

A novel hematopoietic growth factor for primitive hematopoietic progenitor cells, the ligand for the flt3/flk2 receptor, (FL), has been recently purified and its gene has been cloned. In the present study, we investigated the effects of FL on the proliferation and differentiation of normal and leukemic myeloid progenitor cells. We demonstrate that FL is a potent stimulator of the in vitro growth of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), or G-CSF-dependent granulocyte-macrophage committed precursors from Lin- CD34+ bone marrow cells of normal donors. By contrast, FL does not affect the growth of erythroid-committed progenitors even in the presence of erythropoietin. The effect of FL on the proliferation and on the in vitro growth of clonogenic leukemic precursor cells was studied in 54 acute myeloid leukemia (AML) cases. Fresh leukemia blasts from 36 of 45 patients with AML significantly responded to FL without any relation to the French-American-British (FAB) subtype. FL stimulated the proliferation of leukemic blasts in a dose-dependent fashion. Synergistic activities were seen when FL was combined with G-CSF, GM-CSF, IL-3, or stem cell factor (SCF). FL as a single factor induced or increased significantly colony formation by clonogenic precursor cells from 21 of 24 patients with AML. In the presence of suboptimal and optimal concentrations of G-CSF, GM-CSF, IL3, SCF, or a combination of all factors, FL strongly enhanced the number of leukemic colonies (up to 18-fold). We also evaluated the induction of tyrosine phosphorylated protein on FL stimulation in fresh AML cells. We demonstrate that, on FL stimulation, a band of phosphorylated protein(s) of about 90 kD can be detected in FL-responsive, but not in FL-unresponsive cases. This study suggests that FL may be an important factor for the growth of myeloid leukemia cells, either as a direct stimulus or as a synergistic factor with other cytokines.
...
PMID:Effects of human FLT3 ligand on myeloid leukemia cell growth: heterogeneity in response and synergy with other hematopoietic growth factors. 749 67


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---