Gene/Protein Disease Symptom Drug Enzyme Compound
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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)

GMP-140 (P-selectin), a 140-kDa granular membrane glycoprotein localized to the alpha granules of platelets and the Weibel-Palade bodies of endothelial cells, is thought to play an important role in adhesive interactions predominantly between granulocytes, platelets and vascular endothelial cells during inflammation. Although GMP-140 binds to granulocytes, its binding to lymphocytes has not been demonstrated. Using genetically engineered IgG C gamma 1 fusion protein of the extracellular domains of GMP-140, we demonstrate that GMP-140 binds to chronically antigen (Ag)-stimulated CD4+ T cells. Freshly isolated CD4+ T cells did not bind GMP-140, but priming and subsequent stimulation with alloantigen induced and gradually increased expression of GMP-140-reactive structures on their surface. T cells isolated from rheumatoid synovial fluids also exhibited strong binding to GMP-140. The binding of GMP-140 to primed T cells is not influenced by preactivation with phorbol 12-myristate 13-acetate, is almost completely abolished by pretreatment of T cells with neuraminidase or trypsin, and is also strongly inhibited by EDTA, the soluble sulfated glycans dextran sulfate, fucoidan, and heparin, but not by chondroitin sulfates. In spite of its strong binding to Ag-primed T cells, GMP-140 did not modulate the proliferative responses of these cells to various stimuli. However, GMP-140 in conjunction with anti-T cell receptor alpha beta monoclonal antibodies augmented the production of granulocyte-macrophage colony-stimulating factor GM-CSF and inhibited the production of interleukin-8 by Ag-primed T cells without influencing their tumor necrosis factor-alpha production. These results suggest that GMP-140 binds to chronically stimulated CD4+ T cells and differentially modulates their production of proinflammatory cytokines. The ability of Ag-primed T cells to bind GMP-140 may facilitate interactions with activated platelets and endothelial cells affecting the course of inflammation.
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PMID:GMP-140 (P-selectin/CD62) binds to chronically stimulated but not resting CD4+ T lymphocytes and regulates their production of proinflammatory cytokines. 137 17

Post-transcriptional gene regulation plays an important role in the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF). Cytokine secretion by activated lymphocytes or mast cells is preceded by dramatic stabilization of the normally labile GM-CSF mRNA. The 3'-untranslated region of GM-CSF and other labile mRNAs contain the destabilizing motif adenosine-uridine-uridine-uridine-adenosine (AUUUA). We recently identified a cytoplasmic protein denoted the adenosine-uridine binding factor (AUBF) which binds with high affinity and specificity to AUUUA elements in synthetic RNA transcripts. We now demonstrate that AUBF binds specifically to GM-CSF mRNA through the destabilizing AUUUA elements. The formation of AUBF-GM-CSF RNA complexes required calcium or magnesium which were sensitive to EDTA or EGTA. A variety of other divalent metals blocked magnesium-dependent AUBF activity. These observations suggest that AUBF may protect GM-CSF mRNA from rapid degradation and play a crucial role in the expression of cytokine genes.
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PMID:Adenosine-uridine binding factor requires metals for binding to granulocyte-macrophage colony-stimulating factor mRNA. 213 52

Eosinophils are important in antibody-mediated immune defense against parasites based on interaction with Ig receptors (FcR). Of the three classes of IgG FcR in humans, hFc gamma RI, II, and III, solely hFc gamma RII (CD32) is expressed on freshly isolated eosinophils. Despite an expression level similar to that found on monocytes and polymorphonuclear granulocytes, binding activity of hFc gamma RII on eosinophils is constitutively low. Freshly isolated eosinophils had a negligible ability to form rosettes with IgG-sensitized erythrocytes (EA-IgG). Addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) caused an approximately threefold increase in EA-IgG rosettes. This increase was maximal after 35 minutes, and declined upon further incubation at 37 degrees C. Analysis of hFc gamma RII expression levels showed no significant changes and neither was the expression of other hFc gamma R classes induced. Blocking studies with anti-Fc gamma receptor monoclonal antibody (MoAb) proved hFc gamma RII specificity of enhanced IgG complex binding. These phenomena were not restricted to GM-CSF action, because the addition of interleukin-3 or interleukin-5 similarly enhanced EA-IgG binding. The kinetics of activation of hFc gamma RII binding activity were paralleled by the binding of EA-C3bi to CR3 on eosinophils. In contrast to the stable expression of hFc gamma RII during activation with GM-CSF, CR3 expression increased slowly. Ligand binding via both types of opsonin receptors proved receptor specific. However, the kinetics of enhanced binding via hFc gamma RII and CR3 suggested the possibility of a common mechanism underlying the enhancement of ligand binding via hFc gamma RII and CR3. This hypothesis was supported by the fact that binding via hFc gamma RII proved sensitive to both high concentrations of F(ab')2 fragments of anti-CD11b MoAb MO1 and chelation of bivalent cations with EDTA. In conclusion, our studies indicate that cytokines can induce a transient enhancement of hFc gamma RII binding activity. Qualitative, and not quantitative, changes in this receptor appear to underly the modulation of binding activity, which may be linked to changes in CR3 activity.
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PMID:Granulocyte-macrophage colony-stimulating factor induces sequential activation and deactivation of binding via a low-affinity IgG Fc receptor, hFc gamma RII, on human eosinophils. 848 20

Incubation of human neutrophils with 500 pM granulocyte-macrophage colony-stimulating factor (GM-CSF) results in a rapid and time-dependent increase in the phosphorylation of cytosolic phospholipase A2 (cPLA2), which was reflected in a slower electrophoretic mobility of the enzyme. The GM-CSF-induced phosphorylation of cPLA2 was accompanied by a parallel and time-dependent increase in the enzyme activity. Preincubation of neutrophils with the tyrosine kinase inhibitor genistein caused inhibition of the GM-CSF-stimulated phosphorylation and activity of cPLA2. Immunoprecipitation of the enzyme following incubation of neutrophils with [32P]Pi shows that cPLA2 is phosphorylated by GM-CSF. Potato acid phosphatase caused dephosphorylation of the enzyme, indicating that cPLA2 is indeed phosphorylated by GM-CSF. The subcellular distribution of cPLA2 in GM-CSF-stimulated neutrophils revealed that the enzyme resides almost completely in the cytosolic fraction. Addition of Ca2+ to the lysis buffer before homogenization results in the translocation of the phosphorylated and the dephosphorylated forms of the enzyme to the membranes. Translocation of cPLA2 was also achieved after incubation with 0.1 microM N-formylmethionyl-leucyl-phenyl-alanine (fMLP) after GM-CSF stimulation and when neutrophils were challenged with the Ca2+ ionophore A23187. EDTA and EGTA were unable to solubilize the translocated enzyme from the neutrophil membranes, indicating that cPLA2 is attached to the membranes by strong bonds and not merely due to ionic forces exerted by Ca2+. The inability of GM-CSF to promote arachidonic acid mobilization is probably due to the fact that GM-CSF does not cause an increase in intracellular Ca2+, which is necessary for the translocation of the enzyme to the membranes where its substrate(s) reside.
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PMID:Granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes phosphorylation and an increase in the activity of cytosolic phospholipase A2 in human neutrophils. 857 84

A whole-blood model was used to evaluate the effects of temperature and anticoagulant on the expression of activation markers HLA-DR and CD11b on peripheral leukocytes. Venous blood, anticoagulated with either EDTA or heparin, was obtained from six healthy blood donors and 13 hospitalized patients (8 human immunodeficiency virus type 1-seropositive individuals with concurrent pulmonary tuberculosis and 5 patients with pneumonia). A preliminary evaluation was carried out with whole blood from two of the normal donors, and cells were stained immediately for HLA-DR and CD11b markers or stained after incubation at room temperature or 37 degreesC for 18 h with or without the addition of the cytokines gamma interferon (IFN-gamma), granulocyte-macrophage colony-stimulating factor (GM-CSF), IFN-gamma plus GM-CSF, tumor necrosis factor beta, or interleukin-6. Of the cytokines tested, the combination of IFN-gamma and GM-CSF had the most pronounced modulation of marker expression on polymorphonuclear neutrophils (PMN), in particular, HLA-DR expression, which required induction for its detection. These cytokines were therefore used in further evaluations that considered the above-mentioned effects in the presence of disease. Results indicated that the expression of activation markers on PMN and lymphocytes in whole blood are influenced by the temperature of incubation and the choice of anticoagulant and the effects noted were dependent on (i) the particular cell surface marker, (ii) the cell type being studied, and (iii) the presence or absence of disease. It is therefore recommended that ex vivo whole-blood models for evaluating phenotype or immune function be carefully evaluated for the above-mentioned effects.
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PMID:Effects of anticoagulants and temperature on expression of activation markers CD11b and HLA-DR on human leukocytes. 972 38

The aim of the current study was to examine the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the development and differentiation of preimplantation mouse embryos from different strains and under different culture conditions. Embryos from F1 hybrid mice were cultured in a modified G1 medium lacking amino acids and EDTA (simple G1), human tubal fluid medium (HTF) or in G1/G2 sequential media, supplemented with GM-CSF (0, 2, 4, 8, and 16 ng/ml). Embryos from CF1 mice were subsequently cultured in G1/G2 with (5 mg/ml) or without HSA, in the absence or presence of GM-CSF (2 ng/ml). GM-CSF had no effect at any concentration on F1 embryo development and blastocyst cell numbers, irrespective of the culture media used. Similarly, GM-CSF had no effect on CF1 blastocyst development. However, a stimulatory effect of GM-CSF was evident on total blastocyst cell number and ICM development when CF1 embryos were cultured in the absence of HSA. When HSA was present in the media the beneficial effect of GM-CSF was negated. There was no difference in the number of apoptotic cells in CF1 blastocysts when G1/G2 were supplemented with GM-CSF with or without HSA. These data indicate that there is no beneficial effect of supplementing either simple (simple G1 or HTF) or more complete (G1/G2) media with GM-CSF when protein is present in the medium. However, when culture conditions are suboptimal and non-physiological, i.e. the absence of protein, GM-CSF stimulates development of both total cell numbers and ICM development of CF1 blastocysts.
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PMID:Granulocyte-macrophage colony-stimulating factor stimulates mouse blastocyst inner cell mass development only when media lack human serum albumin. 1590 60