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)

Conditioned medium obtained from the adrenocortical LAF1 mouse tumor (Y-1) cell cultures was able to stimulate the proliferation and the differentiation of granulocyte-macrophage precursors in the normal murine bone marrow. Colony-stimulating factor (CSF) was spontaneously produced by Y-1 cells also in serum-free cultures. By two cycles of gel chromatography on Sephadex G-150 of concentrated conditioned medium two peaks of colony-stimulating activity were isolated that corresponded to apparent molecular radii of 100,000 and 29,000, respectively. At this step of purification, the two factors gave a similar dose-response curve, showed a remarkable resistance to the heat treatment and pH changes, and were not extracted by ether. Because Y-1 cells resulted in infection by retrovirus, they provide a useful model to investigate the relations between viral coded information and CSF production.
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PMID:Colony-stimulating factor produced by murine adrenocortical tumor cells. 348 96

A case of pancreatic carcinoma associated with marked eosinophilia is reported. A 71-yr-old man was admitted to hospital because of melena and abdominal pain. The systematic examinations revealed pancreatic adenocarcinoma with multiple metastases (rectum, lung and brain). The leukocyte count was gradually increased and reached up to 81.7 X 10(9)/l, of which 54% consisted of eosinophils. Colony-stimulating factor (CSF) was detected both in the patient's serum and in the tumor extracts by a normal human bone marrow culture system. The colonies which were stimulated with patient's serum largely consisted of granulocyte, granulocyte/macrophage and eosinophil types. These results suggest that blood leukocytosis and eosinophilia were due to a high concentration of plasma CSF, which was probably produced by the tumor cells.
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PMID:Pancreatic carcinoma associated with marked eosinophilia: a case report. 350 Aug 71

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.
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PMID:Human granulocyte-macrophage colony-stimulating factor purified from a Hodgkin's tumor cell line. 353 1

A factor, termed neutrophil alkaline phosphatase-inducing factor (NAP-IF), that has the capacity to increase the NAP activity of granulocytes was characterized by using two samples: cystic fluid (CF) and conditioned medium of a tumor cell line (T3M5). The molecular weight of NAP-IF was shown to be between 13,000 and 45,000, and its isoelectric point was between 5.5 and 6.2. It was sensitive to heat and proteolytic enzymes, but was resistant to DNase and RNase, suggesting that NAP-IF is an acidic protein or glycoprotein. These characteristics of NAP-IF seem to be similar to those of granulocyte-macrophage colony-stimulating factor (GM-CSF) that is also present in the CF. NAP-IF rich fractions obtained by isoelectric focusing from CF were also found to be rich in a subclass of GM-CSF: granulocyte-CSF (G-CSF). Furthermore, a high correlation was noted between the activities of G-CSF and NAP-IF (gamma = 0.798, P less than 0.005). These results suggest that the two activities, i.e., G-CSF and NAP-IF, may be attributable to an identical macromolecule.
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PMID:Characterization of neutrophil alkaline phosphatase-inducing factor (NAP-IF). 387 40

A helper factor (CHF) necessary for the generation of primary allospecific CTL using BALB/c (H-2d) responder spleen cell and x-irradiated RDM4 (H-2k) stimulator tumor cells was obtained from cultures of mouse spleen cells stimulated for the production of secondary anti-Sendai virus CTL and fractionated by gel filtration chromatography to obtain a 30,000 m.w. species (CHF30). DEAE-cellulose chromatography separated CHF activity from the majority of interleukin 1 (IL 1), interleukin 2 (IL 2), granulocyte-macrophage colony-stimulating factor (CSF), and interferon (IFN). Interleukin 3 (IL 3) and CHF co-eluted when this procedure was used. Reverse-phase high performance liquid chromatography (HPLC) of CHF30 with a variety of elution conditions allowed the separation of CHF activity from IL 1, IL 2, IL 3, CSF, and IFN. IL 3 and CSF in the CHF30 preparation were stable at 80 degrees C for more than an hour, whereas CHF activity decreased rapidly during the first 10 min of incubation. Trypsin treatment of the same material showed that CHF activity was resistant to digestion for 40 min, whereas IL 3 and CSF lost most of their activities during the first 5 min of incubation. These results indicate that CHF activity is mediated by molecules biologically and biochemically distinct from the well characterized cytokines.
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PMID:Chromatographic separation from known cytokines of a helper factor necessary for the generation of murine cytolytic T lymphocytes. 619 15

Circulating neutrophil (polymorphonuclear leukocyte levels rise 50-fold in 13762NF tumor-bearing rats in proportion to the tumor's metastatic potential. Purified tumor-elicited neutrophils enhance metastasis of syngeneic tumor cells when co-injected intravenously; however, circulating and phorbol ester-activated polymorphonuclear neutrophils do not. The purpose of this study was to elucidate the source of tumor-elicited neutrophils in metastatic tumor-bearing rats. We examined the bone marrow in rats bearing tumors of poorly, moderately, and highly metastatic cell clones. Marrow from rats with highly metastatic tumors had increased cellularity (100%), myeloid to erythroid ratio (10:1), and megakaryocytes compared with control rats (cellularity, approximately 80%; myeloid to erythroid ratio, 5:1), with marrows from rats with moderately metastatic tumors having intermediate values. This suggested production of a colony-stimulating factor by the metastatic cells. To confirm this, bone marrow colony formation from control and tumor-bearing rats was compared. Colony number increased in proportion to the metastatic potential of the tumor. Conditioned medium from metastatic cells supported growth of the granulocyte-macrophage colony-stimulating factor/interleukin-3-dependent 32Dcl3 cell line, but media from nonmetastatic or moderately metastatic cells did not. Antibodies to murine granulocyte-macrophage colony-stimulating factor neutralized 32Dcl3 growth in tumor cell conditioned medium. These results suggest production of a granulocyte-macrophage colony-stimulating factor or interleukin-3-like activity by highly metastatic 13762NF clones and implicate a possible role for colony-stimulating factors in regulating the metastatic potential of mammary adenocarcinoma cell clones.
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PMID:Highly metastatic 13762NF rat mammary adenocarcinoma cell clones stimulate bone marrow by secretion of granulocyte-macrophage colony-stimulating factor/interleukin-3 activity. 749 92

We studied cytotoxic capabilities of newborn polymorphonuclear leukocytes (PMNs) and monocytes and their enhancement by cytokines and antibodies. Umbilical cord PMNs were assessed for their ability to kill various target cells spontaneously, after activation with phorbol myristate acetate, in the presence of antiserum (antibody-dependent cellular cytotoxicity), and in the presence of dually specific antibody (heteroantibody-mediated cytotoxicity). Target cells included the K562 cell line (natural killer cell target), chicken erythrocytes (CRBCs), and herpes simplex virus-infected CEM cell lines. Newborn PMNs were equivalent to adult PMNs in their cytotoxic capacity in several cytotoxicity assays. Neither adult nor newborn PMNs lyse tumor cell targets (i.e., K562 cells) spontaneously, but both lyse K562 cells following activation with phorbol myristate acetate. Both adult and newborn PMNs lyse CRBCs and herpes simplex virus-infected CEM cells in antibody-dependent cellular cytotoxicity assays, and this lysis could be enhanced by the cytokines granulocyte-macrophage colony-stimulating factor and gamma interferon. PMN heteroantibody-mediated cytotoxicity, resulting from the use of an antibody with dual specificity to CRBCs and immunoglobulin G FcRII, was greater in newborn PMNs than in adult PMNs; however, monocyte heteroantibody-mediated cytotoxicity, resulting from the use of an antibody to CRBCs and monocyte immunoglobulin G FcRI, was lower in newborn monocytes than in adult monocytes. The percentage, but not the density, of PMNs expressing FcRII was significantly reduced in newborn PMNs compared with that in adult PMNs, while the percentages and densities of FcRI expression were equivalent in newborn and adult monocytes. We conclude that the cytotoxic capability in term newborn PMNs is equivalent to that in adult PMNs, that the activity of newborn PMNs can be enhanced by antibody and/or cytokines, and that PMNs can contribute to the newborn's ability to kill virus-infected cells.
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PMID:Comparison of cytotoxic properties of neonatal and adult neutrophils and monocytes and enhancement by cytokines. 749 73

Peripheral blood stem cells (PBSC) are used increasingly as a source of stem cell support following myeloablative therapy. In this report, the results of 33 patients undergoing PBSC transplantation were compared to 17 concurrent patients undergoing autologous bone marrow transplantation (ABMT). PBSC were cryopreserved using 6% pentastarch and 5% dimethyl sulfoxide (DMSO) with noncontrolled-rate freezing. Many patients in the PBSC group were selected because they were excluded as candidates for ABMT due to prior pelvic irradiation, marrow tumor involvement, or other factors. PBSC were mobilized with high-dose cyclophosphamide (CY), CY+granulocyte-macrophage colony-stimulating factor (GM-CSF), or GM-CSF alone. Colony-stimulating factors were not administered after transplantation. A median of 7.4 x 10(8) mononuclear cells (MNC)/kg were collected containing a median of 3.2 x 10(4) granulocyte-macrophage colony-forming units (CFU-GM)/kg and 5.7 x 10(4) burst-forming units (BFU-E)/kg. After thawing, CFU-GM recovery was 67% and BFU-E recovery was 59%. The thawed, pooled PBSC contained 6.4 x 10(6) CD34+ cells/kg. The entire PBSC volume (median 870 mL) was infused over a median of 157 minutes. PBSC patients required a median of 15 days to achieve an ANC of 500/microL and 22 days for a platelet count of 50,000/microL. Neutrophil recovery was inversely correlated with the number of harvested progenitor cells (p = 0.014); the time to achieve a platelet count of 50,000/microL was inversely associated with CD34+ cells/kg (p = 0.005). PBSC transplant patients achieved an ANC of 500/microL 6 days faster (p < 0.05) and had a 10-day shorter hospitalization (p < 0.05) than ABMT patients. Use of noncontrolled-rate cryopreserved PBSC is associated with faster engraftment and shorter hospital duration than ABMT.
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PMID:Engraftment with peripheral blood stem cells using noncontrolled-rate cryopreservation: comparison with autologous bone marrow transplantation. 750 92

Cytotoxic T-lymphocytes (CTLs) specific for autologous human squamous cell cancer of the lung were generated by stimulation of peripheral blood lymphocytes with autologous tumor cells in vitro. The CTL line was >97% CD3+, CD8+, CD16- and produced tumor necrosis factor-alpha, gamma-interferon, and granulocyte-macrophage colony-stimulating factor after stimulation with autologous tumor. The CTLs lysed autologous tumor but failed to recognize autologous or histocompatibility leukocyte antigen-matched lymphoid cells, K562, or allogeneic tumor cells of several histological types. Antibody-blocking studies suggested that the CTLs recognized one or more antigens presented by the class I major histocompatibility complex molecule Aw68. To characterize these antigens further, histocompatibility leukocyte antigen Aw68 molecules were extracted from the squamous cell cancer of the lung tumor line by immunoaffinity chromatography, and the associated peptides were eluted in acid and separated by reversed-phase high-performance liquid chromatography. Reconstitution of the CTL epitope was evaluated by adding these peptides to autologous Epstein-Barr virus-transformed B-cells. Two peaks of reconstituting activity were observed, suggesting that these CTLs recognize at least two Aw68-associated peptides. This study confirms the existence of a CTL response against autologous human squamous cell cancer of the lung and suggests that this CTL response is directed against peptide epitopes presented by the class I major histocompatibility complex molecules. It is anticipated that this approach will permit identification of peptide epitopes for lung cancer-specific CTLs.
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PMID:Cytotoxic T-lymphocyte response to autologous human squamous cell cancer of the lung: epitope reconstitution with peptides extracted from HLA-Aw68. 751 55

We established a human bone marrow stromal cell line (Saka) by infecting marrow adherent cells from semisolid marrow cultures with a recombinant simian virus-40 (SV40) virus. The cells expressed SV40 large tumor antigen, had a fibroblast-like shape, and expressed fibronectin and vimentin. They did not contain detectable alkaline phosphatase activity; express myeloid, lymphoid, or factor VIII-associated antigens; or develop adipocyte-like characteristics with dexamethasone treatment. Polymerase chain reaction analysis of Saka cell RNA detected expression of messenger RNAs for interleukin-6 (IL-6), IL-1 beta, granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, stem cell factor, and the 1,25-dihydroxyvitamin D3 receptor. Coculture of Saka cells with human marrow mononuclear cells enhanced formation of osteoclast-like multinucleated cells (MNC) in long term human bone marrow cultures. These MNC expressed calcitonin receptors and formed resorption lacunae on dentine. In contrast, coculture of marrow mononuclear cells with other SV40-transformed human marrow stromal cell lines did not increase MNC formation. Conditioned medium from Saka cells or coculture of bone marrow and Saka cells separated by a Millipore membrane did not enhance MNC formation. Addition of a neutralizing antibody to IL-6 or IL-1 beta blocked the effects of Saka cells on MNC formation. These results suggest that marrow stromal cells enhance osteoclast formation in part through direct cell to cell contact and production of IL-6 and/or IL-1 beta.
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PMID:Development and characterization of a human marrow stromal cell line that enhances osteoclast-like cell formation. 753 99


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