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)

Previous in vitro studies with recombinant human Interleukin 3 (IL-3) in serum-replete culture conditions suggested that IL-3 induced the complete differentiation of multipotent and both, erythroid and myeloid progenitor cells. In contrast, serum-free cultures have shown that alone, IL-3, and to a lesser extent granulocyte-macrophage colony-stimulating factor (GM-CSF), are inadequate differentiation stimuli. However, in combination with the lineage-specific growth factors, erythropoietin, granulocyte colony stimulating factor (G-CSF), and macrophage CSF (M-CSF), complete recovery of erythroid, granulocyte, and macrophage colonies, respectively, was obtained. GM-CSF is produced by a variety of mesenchymal cells as well as monocytes and T lymphocytes; in contrast, IL-3 production appears to be restricted to lectin stimulated T lymphocytes. These studies indicate that the CSFs may be more effective in vivo when used as combinations rather than as single factors. The restricted production of IL-3 by activated T cells suggests that IL-3 may be released during infections and may play an important role during stress.
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PMID:The biology of the colony stimulating factors. 326 67

Fifty-five hematopoietic cell lines, including 19 T-, 16 B-, 5 pre-B-, 5 non-T non-B-, 1 erythroid, and 9 myeloid-monocytoid cells, were screened for production of human hematopoietic survival and stem cell growth factor (SCGF) by enzyme immunoassay using anti-SCGF monoclonal antibody. The KPB-M15 myeloid cell line constitutionally secreted a considerable quantity of SCGF, while other T- or myeloid-monocytoid cell lines did not secrete SCGF. Other biomaterials investigated were fetal calf, horse, and human serum; granulocyte-macrophage colony-stimulating factor and erythropoietin preparations; human placental conditioned medium; lectin (phytohemagglutinin, concanavalin A, and pokeweed mitogen); and mixed leukocyte reaction-stimulated leukocyte-conditioned medium. SCGF was detected only in human placental conditioned medium. SCGF produced by the KPB-M15 cells was a protein with a molecular weight of 20,000. The molecule, highly purified by immunoadsorbent affinity chromatography, retained SCGF activity in vitro, e.g., erythroid burst-promoting activity and granulocyte-macrophage-colony potentiation. With the availability of purified SCGF, it is now possible to study in detail the mechanisms regulating hematopoietic stem cells.
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PMID:Production of human hematopoietic survival and growth factor by a myeloid leukemia cell line (KPB-M15) and placenta as detected by a monoclonal antibody. 330 20

Biologic and biochemical properties of a human basophil-like cell promoting activity (BaPA), which induces growth of metachromatically staining cells from normal bone marrow cells in a liquid culture system have been examined. In order to study this T cell factor, an assay was developed based on the intracellular histamine content of the cultured human bone marrow cells. Many lymphokines, including granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, interleukin 1 alpha and 1 beta, interleukin 2, and interferon-alpha and gamma, did not exhibit any significant activity in the assay. By employing this assay, BaPA was purified approximately 500-fold from lectin-stimulated spleen cell-conditioned medium. BaPA has a molecular weight of 23,000 on high performance liquid chromatography gel filtration and displays isoelectric points between 5.8 and 7.3. It is heat stable up to 80 degrees C for 30 min and resistant to 6 M guanidine hydrochloride, whereas it is rather sensitive to sulfhydryl reagents. BaPA has no stimulating activity on mouse bone marrow cells.
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PMID:Characterization of a human basophil-like cell promoting activity. 333 79

Colony-stimulating factors (CSFs) are glycoproteins that stimulate the growth of hematopoietic progenitors and enhance the functional activity of mature effector cells. Human granulocyte/macrophage colony-stimulating factor (GM-CSF) is a 22-kDa glycoprotein that stimulates the growth of myeloid and erythroid progenitors in vitro and increases the responsiveness of neutrophils, monocytes, and eosinophils to physiologic stimuli. Elucidation of the cell and tissue sources of CSFs, as well as study of their regulation of expression, is required to understand their role in physiologic and pathophysiologic states. An extensive survey of normal and neoplastic human tissues did not reveal constitutive production of detectable levels of GM-CSF mRNA in any of the 64 samples studied. Antigen- or lectin-activated T lymphocytes have been shown to produce GM-CSF; therefore, to elucidate the genetic sequences required, we constructed recombinant plasmids containing 5' flanking DNA of the GM-CSF gene linked to the marker chloramphenicol acetyltransferase gene. The recombinant constructs were transfected into a human T-cell leukemia virus type I (HTLV)-infected T-lymphoblast cell line that can be stimulated to produce high levels of GM-CSF. We show here that the 5' flanking sequences of the GM-CSF gene can direct increased expression of the chloramphenicol acetyltransferase gene in activated T-lymphoblast cells.
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PMID:Regulation of expression of human granulocyte/macrophage colony-stimulating factor. 349 Jun 69

The effects of pure and crude human urinary erythropoietin, crude sheep plasma erythropoietin and other growth factors on the incorporation of labeled thymidine were studied using spleen cells from mice previously treated with phenylhydrazine hydrochloride. Erythropoietin at 400 mU/ml caused a 40-80 fold increase in the incorporation of the labeled nucleoside. The slope of the dose-response curve found for pure erythropoietin was not significantly different from that found for a crude urinary erythropoietin preparation or for crude sheep plasma erythropoietin. Colony-stimulating factor, interleukin 2, interleukin 3 and the lectin, concanavalin A were also stimulatory but at concentrations from one hundred to one million times higher than that found for erythropoietin.
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PMID:The effect of erythropoietin and other factors on DNA synthesis by mouse spleen cells. 660 86

Isoelectric focusing demonstrated that T cell growth factor (TCGF), T cell replacing factor (TRF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) derived from concanavalin A-stimulated T cell hybridomas and spleen cells are heterogeneous with respect to charge. The spleen cell-derived TCGF and TRF activities focused with isoelectric points (pI) between 3.5 and 6.5 whereas the range for GM-CSF activity was broader (pI, 3.5 to 8.0). The T cell hybridoma-derived activities were slightly more acidic. Neuraminidase treatment of both hybridoma 123 and spleen cell-derived material resulted in a major peak of each activity (TRF/TCGF pI, 4.9; GM-CSF pI, 4.7). Neuraminidase treatment of hybridoma T6-derived material resulted in peaks of TRF and TCGF around 6.0 as well as one around 5.0, suggesting that this charge heterogeneity was due to causes other than variations in the level of sialic acid on the relevant molecules. Tunicamycin-treated spleen cells or hybridoma 123 cells released biologically active TCGF, TRF, and GM-CSF. Each of these three activities from tunicamycin-treated spleen cells focused with pI around 5.0. A major fraction of TRF, TCGF, and GM-CSF activities bound to wheat-germ agglutinin. GM-CSF also bound to concanavalin A and lentil lectin. These results suggest that the molecules responsible for TCGF, TRF, and GM-SCF activities are glycosylated and that the observed heterogeneity in charge and lectin-binding characteristics is due in part to variable glycosylation. Glycosylation was not critical for any of the three biologic activities. No conclusive separation of TRF and TCGF activities was observed in these experiments although GM-CSF differed from TRF and TCGF in that it bound to Concanavalin A.
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PMID:Biochemical characterization of regulatory factors derived from T cell hybridomas and spleen cells. II. Evidence for glycosylation of T cell growth factor, T cell replacing factor, and granulocyte-macrophage colony-stimulating factor. 697 70

The phenotype and functional characteristics of skin-infiltrating lymphocytes in beta-lactam antibiotic-induced vesiculobullous exanthemas were studied in vivo and in vitro. Immunohistochemical analysis demonstrated that CD8+ T lymphocytes were the predominant epidermal T-cell subset in these reactions. Epidermal T lymphocytes were isolated and expanded for in vitro studies. Fluorescence-activated cell sorter analysis showed the majority of epidermal T cells to be CD3+, T-cell receptor alpha/beta+, CD4-, CD8+, and HLA-DR+, which correlated with the predominance of epidermal CD8+ T lymphocytes found in situ. Three CD8+ epidermal T-cell clones derived from cutaneous lesions proliferated in response to penicillin-pulsed autologous antigen-presenting cells but not allogeneic antigen-presenting cells, indicating that those clones were antigen and major histocompatibility complex specific. All T-cell clones produced significant amounts of interleukin-2, interferon-gamma, and granulocyte-macrophage colony-stimulating factor. Additionally, the T-cell clones displayed cytotoxicity against epidermal cells in lectin-mediated cytotoxicity and against B-cell lines in T-cell receptor-triggered cytotoxicity. These data demonstrate the presence of epidermal drug-specific CD8+ T cells in bullous drug reactions. Because these CD8+ T cells have a cytotoxic potential, they may contribute to the necrosis of keratinocytes associated with drug-induced blister formation.
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PMID:Predominance of epidermal CD8+ T lymphocytes in bullous cutaneous reactions caused by beta-lactam antibiotics. 824 7

An adult T cell leukemia cell line, HIL-3, constitutively secretes a factor which induces the phenotypical and functional eosinophilic differentiation of a human eosinophilic leukemia cell line, EoL-1. Biochemical characteristics of the factor, termed eosinophilic leukemia cell differentiation factor (ELDF), were examined. ELDF was precipitated by 35 to 65% saturated ammonium sulfate from the culture supernatants of HIL-3 cells (HIL-3 sup). ELDF was eluted in a peak corresponding to a molecular weight of 30 to 40 kd by gel filtration. Isoelectric focusing in the Rotofor showed that ELDF had isoelectric points of 5 to 6. ELDF was trypsin-sensitive and stable to heat treatment at 65 degrees C for 30 minutes but labile at 80 degrees C or pH lower than 3. Half of the activity adhered to lentil-lectin but not to Con-A, indicating that a part of ELDF is glycoprotein with an N-linked carbohydrate moiety, which did not seem to be essential for ELDF activity. The biochemical characteristics of ELDF and blocking experiments using cytokine-specific neutralizing antibodies suggest that ELDF is different from gamma-interferon (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-5 (IL-5) and interleukin-2 (IL-2), which may exist in HIL-3 sup, and that ELDF may be a previously unrecognized leukemia differentiation factor.
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PMID:Characterization of an eosinophilic leukemia cell differentiation factor (ELDF) produced by a human T cell leukemia cell line, HIL-3. 850 May 76

The expression of galectin-3 (formerly known as IgE-binding protein or Mac-2) in rat bone marrow (BM) was investigated by FACS, immunocytochemical and immunoblot analysis. The functional significance of rat recombinant galectin-3 on mouse recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF)-driven proliferation of macrophage progenitors and gene transcription was further examined. Immunocytochemical analysis of in situ BM sections demonstrated galectin-3 in myelopoietic cells and surrounding stroma, whereas erythropoietic and lymphopoietic environments essentially lacked galectin-3 expression. FACS analysis demonstrated that incubation of freshly isolated BMC with lactose, a competing ligand for galectin-3 binding to glycoconjugates, decreased binding of antigalectin antibodies to cells primarily expressing the myeloid antigen recognized by mAb His-54. Similarly, lectin-mediated binding of exogenous galectin-3 to myeloid lineage cells was also demonstrated. Immunoblot analysis of BM eluates demonstrated galectin-3 both in the extracellular matrix and in a lactose elutable form, bound to the surface of BMC. [3H]Thymidine incorporation studies on BMC cultured in the presence of galectin-3 demonstrated suppression of GM-CSF-induced proliferation by galectin-3. In addition, differential display analysis of immediate early gene expression in BMC cultured in the presence of galectin-3 revealed a 76.2% inhibition of GM-CSF-induced gene transcription by galectin-3 assessed by the number of PCR-fragments generated. Our data suggest a role for galectin-3 in the organization of myelopoietic compartments in rat BM and regulation of the action of growth factors on myelopoietic precursor cells.
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PMID:Galectin-3 inhibits granulocyte-macrophage colony-stimulating factor (GM-CSF)-driven rat bone marrow cell proliferation and GM-CSF-induced gene transcription. 924 34

In this study, we analyzed the expression and function of the lymphocyte surface lectin NKRP1A on peripheral blood monocytes (Mo) or Mo and dendritic cells (DC) derived from thymic and bone marrow precursors. De novo expression of NKRP1A and CD14 molecules was detected upon culture of CD2- CD3- CD14- CD16- CD1a- NKRP1A- immature thymic precursors for 7 days in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF). Under these culture conditions, by day 21, a fraction of cells had lost CD14 and acquired both CD80 (B7.1) and CD86 (B7.2) molecules. These cells displayed a DC-like morphology and were surface NKRP1A positive. CD34+ NKRP1A- CD14- precursors, isolated from bone marrow and cultured in the presence of GM-CSF, also expressed both NKRP1A and CD14: these antigens were newly expressed on about one third of cells which had lost the CD34 precursor marker. In addition, NKRP1A was constitutively present on resting CD14+ peripheral blood Mo. When these cells were cultured in the presence of GM-CSF, the resulting DC population retained the expression of NKRP1A and acquired CD80, while they lost the CD14 antigen. Functional analysis revealed that the engagement of NKRP1A molecule leads to a strong intracellular calcium ([Ca2+]i) increase both in resting peripheral blood Mo and in vitro-derived DC. [Ca2+]i increase was mainly due to extracellular calcium influx, as it was completely abrogated by the addition of EGTA. More importantly, the engagement of the NKRP1A molecule induced interleukin (IL)-1 beta and IL-12 production by resting Mo and DC, respectively. Altogether these data indicate that NKRP1A lectin is present at the surface of Mo and DC and may play a relevant role in the activation and function of both cell types.
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PMID:Expression and function of NKRP1A molecule on human monocytes and dendritic cells. 939 25


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