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)

Culture of WEHI-3B myelomonocytic leukemic cells in semi-solid agar medium containing serum from mice injected with endotoxin serum (ES) led to the development of maturing granulocytes and macrophages in most leukemic colonies. ES contains high levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), a regulator known to stimulate differentiation of these leukemic cells, but an antiserum which neutralized greater than 85% of the GM-CSF in ES did not suppress the differentiation-inducing activity of ES on WEHI-3B cells. The active factor in endotoxin serum stimulating differentiation in WEHI-3B leukemic cells (GM-DF) was separated from most of the GM-CSF by gel filtration using Ultrogel AcA44. The residual CSF associated with the GM-DF appeared to stimulate selectively granulocytic colonies. Disproportionation of GM-DF and GM-CSF was observed in ES fractions obtained using concanavalin-A/Sepharose chromatography: none of the GM-DF bound to this matrix, whereas 40% of the GM-CSF bound and was eluted with competing alpha methylglucopyranoside. Although no separation of GM-CSF and GM-DF was obtained using DEAE-Sepharose, non-isoelectric focusing in amphoteric buffers indicated charge differences between the differentiation factor and several sub-species of GM-CSF. Sequential purification of GM-DF from ES using 40 - 70% ammonium sulfate precipitation gel filtration and phenyl-Sepharose chromatography resulted in a 25-fold purification. In all fractionation procedures used, a sub-species of GM-CSF, stimulating granulocyte colony formation, was consistently associated with partially purified GM-DF, but some subspecies of GM-CSF clearly lacked any capacity to induce differentiation in the leukemic cells. The observations suggest that the factor in post-endotoxin serum most efficient in enforcing differentiation in myelomonocytic leukemic cells may be a subset of GM-CSF molecules with a selective capacity to stimulate granulocyte colony formation by normal cells.
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PMID:Characterization of a serum factor stimulating the differentiation of myelomonocytic leukemic cells. 697 58

Interleukin 2 (IL-2), produced with and without co-stimulation by the Burkitt's lymphoma line Daudi, was purified 37,000-fold to apparent homogeneity from lymphocyte conditioned medium by (NH4)2SO4 precipitation, DEAE-cellulose ion-exchange chromatography, gel filtration, and chromatography on blue agarose and on Procion-red agarose. The purified IL-2 showed a 10(6) U/mg protein sp act. IL-2 produced in the absence of Daudi cells had a mol wt of 26,000 as measured by gel filtration and an isoelectric point of 6.7. This IL-2 showed a 16,000 and 17,000 mol wt in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). IL-2, produced in the presence of Daudi cells (10(6)/ml), showed a mol wt of approximately 14,000, as measured by both gel filtration and SDS-PAGE, and an isoelectric point of 8.1. The purified IL-2 lacked detectable interferon (alpha and gamma), granulocyte-macrophage colony-stimulating factor, B cell growth factor, T cell-replacing factor, and thymocyte-differentiating activity and was free of any contaminating proteins as judged by silver staining in SDS-PAGE. All three molecular forms of IL-2 were biologically active at concentrations of 10(-11) - 10(-10) M, supporting the growth of human and murine cytotoxic T cell lines.
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PMID:Purification of human interleukin 2 to apparent homogeneity and its molecular heterogeneity. 698 Feb 56

Human polymorphonuclear neutrophils exhibit a low level of the microtubule-associated protein kinase (MAPK) activity. This enzymic activity is enhanced up to 3-fold upon cell stimulation with the human haematopoietic hormone granulocyte-macrophage colony-stimulating factor (GM-CSF). This is demonstrated both in whole-cell lysates and in DEAE-anion-exchange semi-purified fractions prepared from GM-CSF-stimulated neutrophils, by assaying the kinase activity against either myelin basic protein or a phosphoacceptor peptide that bears the specific phosphorylation site of the MAPK natural substrate. Similarly, phosphorylation of MAPK in tyrosine residues, as found in immunoblots using anti-phosphotyrosine antibodies, follows similar time- and dose-response curves as the kinase activation. Pretreatment of the cells with the tyrosine kinase inhibitor genistein abrogates the above-mentioned effect, whereas the phosphatase inhibitor okadaic acid enhances both the basal and the GM-CSF-stimulated kinase activities. Likewise, MAPK tyrosine phosphorylation is diminished in genistein-treated neutrophils, and enhanced in okadaic acid-treated cells. We conclude that MAPK activity is present in human neutrophils, and that it is stimulated by GM-CSF. This stimulation of the activity is most likely due to the phosphorylation of MAPK in tyrosine residues triggered upon binding of GM-CSF to its receptors.
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PMID:Direct stimulation by tyrosine phosphorylation of microtubule-associated protein (MAP) kinase activity by granulocyte-macrophage colony-stimulating factor in human neutrophils. 768 11

Macrophages are putative target cells for expressing an exogenous gene with therapeutical effects. Knowing that macrophages express membrane lectins mediating endocytosis of their ligands, DNA/glycosylated polylysine complexes were used to transfect human blood monocyte-derived macrophages. Monocytes from human peripheral blood were matured in culture for 7 days to differentiate into macrophage-like cells in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF). Adherent cells, which displayed characteristic macrophage markers, CD 14, CD 11b, HLA-DR, and HLA-ABC antigens and mannose receptor, were transfected by DNA/glycosylated polylysine complexes in the presence of chloroquine. The luciferase reporter gene expression was maximal 24 hr after transfection with a DNA/mannosylated polylysine complex and by using plasmids in which the promoters (either the long terminal repeat of the human immunodeficiency virus or the human cytomegalovirus) drove the luciferase gene expression. Luciferase gene expression was lower when the promoter was the early region of the large T antigen of SV40 virus. Transfection mediated by DNA/mannosylated polylysine complexes was much more efficient than with DEAE-dextran or lipofectin. The possibility of transferring and expressing an exogenous gene into macrophage-like cells by using a nonimmunogenic synthetic vector as a DNA carrier opens new ways to develop nonviral gene therapy strategies.
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PMID:Gene transfer by DNA/glycosylated polylysine complexes into human blood monocyte-derived macrophages. 891 94


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