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)

We have studied the role of murine eosinophils as antigen-presenting cells (APC). Eosinophils have several characteristics that support the hypothesis of its function as potential APC: they have phagocytic capacity, express adhesion molecules and major histocompatibility complex (MHC) class II antigens and can produce and release interleukin-1 (IL-1). We have obtained several T cell clones specific for Mesocestoides corti antigens and used T cell hybridoma specific for ovalbumin (OVA) to test this hypothesis. Granulocyte-macrophage colony-stimulating factor-activated pure eosinophils (99.9%), express class II antigens and are able to present M. corti antigens to specific T cell clones or OVA to T cell hybridoma 3DO 11.10, inducing the proliferation of T cell clones and IL-2 release by the T cell hybridoma. Proliferation of T cells clones is dependent on the number of eosinophils used as APC. We have compared the efficiency of the same number of macrophages and eosinophils as APC, and have found that macrophages are more efficient than eosinophils. Lysosomotropic agents, such as chloroquine and ammonium chloride, that inhibit antigen processing, impaired eosinophil presentation. This presentation is restricted by MHC class II and inhibited by anti-I-Ad monoclonal antibody. The present study provides clear evidence of APC function for eosinophils. Our investigation points to a new role for eosinophils in the immune response.
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PMID:Eosinophil as antigen-presenting cell: activation of T cell clones and T cell hybridoma by eosinophils after antigen processing. 162 30

It has long been known that complex interactions occur between tumors and normal host immune cells. The human melanoma cell line A375 has been used previously as an indicator cell for tumor cell cytotoxicity mediated by monocytes. During other studies on this tumor cell line, we noted that the conditioned media harvested from A375 cultures induced both the human monocytoid cell line U937 and human blood monocytes to release the cytokine tumor necrosis factor (TNF). We characterized this tumor factor which induced TNF release by monocytic cells. Purification was performed using ammonium sulfate precipitation, ion exchange (DEAE) chromatography, gel filtration, and reversed-phase high performance liquid chromatography. The factor copurified with granulocyte-macrophage colony-stimulating factor (GM-CSF). The purified material caused the release of TNF by U937 cells and stimulated formation of granulocyte-macrophage colonies in methyl cellulose. TNF release by U937 cells in response to A375-conditioned medium was inhibited by neutralizing antibodies to GM-CSF. The TNF-inducing activity in A375-conditioned medium was completely removed by an anti-GM-CSF affinity column. Western blotting using antibodies to GM-CSF confirmed a single Mr27,000 band in A375-conditioned medium. We found that recombinant human GM-CSF stimulated TNF production by the same cells as the tumor-conditioned medium. These data show that A375 human melanoma cells produce GM-CSF, which in turn causes TNF production by cells in the monocyte lineage. The combination of GM-CSF production by the tumor and TNF production by immune cells may influence not only tumor growth but also some of the paraneoplastic syndromes associated with malignancy such as hypercalcemia, cachexia and leukocytosis.
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PMID:Stimulation of tumor necrosis factor release from monocytic cells by the A375 human melanoma via granulocyte-macrophage colony-stimulating factor. 218 30

We have purified and further characterized a histamine releasing factor (HRF) derived from human mononuclear cells using gel-filtration HPLC, reverse-phase HPLC, anion exchange chromatography, and elution from SDS gels after electrophoresis. Considerable heterogeneity is seen, far exceeding that published in prior reports. Gel filtration HPLC yielded a major peak at molecular weight 30,000 and minor peaks at 50,000 and 12,000. Reverse-phase HPLC gave one major fraction in the void volume and an eluted peak at 50-60% acetonitrile. Accell QMA anion exchange HPLC revealed three peaks of activity; one in the void volume similar to that published previously using QAE-Sephadex, and peaks that eluted at 0.5 and 0.8 M ammonium acetate, respectively. Electroelution following SDS-PAGE yielded peaks at MW 12,000 and 15-17,000 plus variable peaks at 25-27,000, 31-34,000, and 80-90,000 D. Using a combination of the aforementioned procedures, we have purified molecular species of HRF at 41,000 and 17,000 D to apparent homogeneity, as judged by SDS PAGE and autoradiography. Since human interleukin 3 and granulocyte-macrophage colony-stimulating factor possess histamine-releasing capability, it is clear that multiple cytokines can share this activity. However, the major HRF we isolate from human mononuclear cells appears, thus far, to be unique.
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PMID:Purification and further characterization of human mononuclear cell histamine-releasing factor. 246 21

Sublethally irradiated CBA/J mice injected with lymph node cells (LNC) of C3H/He mice exhibit aplastic anemia within 3 weeks. Aplastic anemia plasma (AAP) from these mice was found to inhibit granulocyte-macrophage colony (GM-CFU) formation. This inhibitory action was not strain specific and was not generated in donor:host combination involving other strains. AAP also inhibited the formation of colonies derived from leukemic cell lines. Though this activity inhibited GM-CFU, it did not affect erythroid colony formation. Two experiments were performed to examine the mechanism of inhibition. Superoptimal concentrations of recombinant mouse granulocyte-macrophage colony-stimulating factor (GM-CSF) did not reverse AAP-induced inhibition of colony formation. Bone marrow cells preincubated with AAP for 24 h and washed were unchanged in their ability to form GM-CFU colonies. Thus, the inhibitory activity acted neither as a competitive nor a cytotoxic agent. Interferons and certain prostaglandins, known to inhibit colony formation, were not found in active concentrations in AAP. The inhibitory activity of AAP was heat stable, nondialyzable, inextractable with chloroform, precipitable with 50% ammonium sulfate, and had a molecular weight of 100,000 daltons. In contrast, control plasma from mice given only sublethal irradiation and injected with saline had significantly less inhibitory activity, which was not heat stable and was extractable with chloroform. Thus, LNC in certain host mouse strains generate a plasma activity that can inhibit the formation of normal and leukemic GM-CFU colonies.
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PMID:Inhibitor of granulocyte-macrophage colony formation in plasma of mice rendered aplastic by allogeneic lymph node cells. 246 13

Recently, several human bone marrow stromal cell lines have established and produced hematopoietic growth factors. One of these factors, a burst-promoting activity (BPA), was purified from 6 liters of serum-free conditioned medium cultured from stromal cell line KM-102, which was stimulated by phorbol myristate acetate (PMA) and calcium ionophore A23187. This stimulation induced 60 times more production of BPA than the unstimulated control culture. BPA was purified 4000-fold by sequential fractionation using ammonium sulfate precipitation, anion-exchange and lentil lectin affinity chromatographies, high performance gel filtration chromatography, and reversed phase high performance liquid chromatography. Purified BPA gave a single broad band of protein with a molecular weight of approximately 18 kd, as assessed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The concentration required for half maximal growth of early erythroid colonies was estimated as 10 pg/ml or 0.6 pM. At a higher concentration (125 pg/ml) this factor also stimulates the growth of granulocyte, macrophage, and eosinophil colonies in agar culture. The profile of amino acid composition is very similar to that of the human granulocyte-macrophage colony-stimulating factor (GM-CSF) deduced from its complementary DNA sequence. The result of amino-terminal sequence analysis strongly suggests that the purified material consists of GM-CSF and tetrapeptide-deleted GM-CSF. Moreover, antibody against GM-CSF completely neutralized the biological activities of this factor. These results indicate that the human bone marrow stromal cell line secretes GM-CSF as a burst-promoting activity and GM-CSF may play a significant role in the interaction between stem cells and stromal cells in the hematopoietic microenvironment.
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PMID:A burst-promoting activity derived from the human bone marrow stromal cell line KM-102 is identical to the granulocyte-macrophage colony-stimulating factor. 313 50

A simple two-step method involving ammonium sulfate precipitation followed by hydrophobic chromatography is described for the separation of T cell growth factor (TCGF) from a number of other factors contained in medium conditioned by concanavalin A-stimulated spleen cells. Thus, granulocyte-macrophage colony-stimulating factor, P cell-stimulating activity, pluripotential stem cell-supporting activity and interferon activity were not detected in TCGF partially purified by these steps. T cell-replacing factor co-purified with TCGF. Macrophage activity factor (MAF) co-purified with TCGF, but the ratio of MAF to TCGF activities was reduced more than 20-fold relative to that in crude conditioned medium. All of the factors were present in the 50-80% saturated ammonium sulfate fraction, however, levels of concanavalin A were reduced by 98% in this step. TCGF, separated in this way from these other regulatory factors will be useful in experiments analyzing the actions of TCGF on mixed populations of cells.
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PMID:Preparation of T cell growth factor free from interferon and factors stimulating hemopoietic cells and mast cells. 618 27

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

We describe the molecular characteristics of T cell growth factor (TCGF), T cell replacing factor (TRF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) produced by a T cell hybridoma after stimulation with concanavalin A (Con A). All three activities could be separated from Con A itself by ammonium sulfate precipitation. The TRF and TCGF activities had a m.w. of 35,000 to 40,000 on gel filtration in phosphate-buffered saline (PBS). Their m.w. were about 30,000 under dissociating conditions in guanidine hydrochloride and about 35,000 to 40,000 under disulfide reducing conditions, suggesting the molecule(s) lacked noncovalent or disulfide-linked subunit structure. GM-CSF had a m.w. of 25,000 to 30,000 by gel filtration in PBS and about 23,000 in guanidine hydrochloride. TRF and TCGF on the one hand and GM-CSF on the other could be distinguished by the criteria of m.w., relative heat sensitivity, and hydrophobic chromatography. TCGF could not be separated from TRF by any of these methods. In terms of all the above properties, factor derived from the T cell hybridoma and spleen cells appeared identical.
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PMID:Biochemical characterization of regulatory factors derived from T cell hybridomas and spleen cells. I. Separation of T cell growth factor and T cell replacing factor from granulocyte-macrophage colony-stimulating factor. 697 69

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

The immunomodulator ammonium trichloro(dioxyethylene-0-0')tellurate (AS101) has previously been found by us to have radioprotective properties when injected into mice before sublethal and lethal doses of irradiation. AS101 also was found to protect mice from hematopoietic damage caused by various chemotherapeutic drugs. Based on these findings, phase II clinical trials with cancer patients treated with AS101, in combination with chemotherapy, are currently underway. In the present study, we wanted to assess the role of several cytokines in the radioprotection conferred by AS101. We show that the administration of neutralizing antibodies against interleukin-1 (IL-1) receptor, IL-6 receptor, IL-6, tumor necrosis factor (TNF), or stem cell factor (SCF) completely abrogates the ability of AS101 to increase the survival of lethally irradiated mice. Moreover, the injection of each of these antibodies reduces the ability of AS101 to increase the number of BM, spleen cells, and the number of circulating neutrophils, lymphocytes, and platelets in irradiated mice. In addition, these antibodies abrogate the enhancing effect of AS101 on the secretion of IL-3, IL-6, and granulocyte-macrophage colony-stimulating factor, all of which decrease significantly in sublethally irradiated mice. By contrast, the injection of anti-IL-2 receptor antibody or control Igs to AS101-treated mice does not interfere with the radioprotective effects of the compound. These results suggest a role for IL-1, IL-6, TNF alpha, and SCF in the radioprotective effect of AS101. Because cytokine toxicity remains a significant concern, the clinical application of AS101, which has no toxicity, is particularly valuable.
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PMID:Role of endogenous cytokines secretion in radioprotection conferred by the immunomodulator ammonium trichloro(dioxyethylene-0-0')tellurate. 788 74


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