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)

Due to its similar biological activities to interleukin 10 (IL-10), Epstein-Barr virus (EBV) BCRF1 gene product (viral IL-10: vIL-10) has recently been recognized as an analogue of authentic IL-10. Preincubation of human monocytes with vIL-10, like human IL-10, induced smaller amounts of interferon-gamma (IFN-gamma) mRNA in activated human peripheral blood mononuclear cells (PBMNCs) than nonpreincubation, indicating that vIL-10 acts principally on monocytes. Since the activation of monocytes and their generation of oxidative products are regulated by various cytokines, we examined the effects of vIL-10 on superoxide anion (O2-) production by human PBMNCs and monocytes. Not only PBMNCs but also monocytes preincubated with vIL-10 showed a smaller production of O2-. Inhibition was achieved in a dose-dependent fashion and increased gradually after incubation with vIL-10. Additions of IFN-gamma, macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF), which prime monocyte activation and induce O2- production, were also affected by the reciprocal effect of vIL-10. Thus, vIL-10 production by EBV-infected cells may be involved in the development of EBV-related disorders.
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PMID:Epstein-Barr virus BCRF1 gene product (viral interleukin 10) inhibits superoxide anion production by human monocytes. 133 11

Basophil chemotactic activity (BCA) of eight recombinant human (rh) cytokines was examined. Highly purified basophils were obtained by Percoll discontinuous gradients, followed by negative selection using flow cytometry. Then BCA was measured by means of modified Boyden chamber method. Both interleukin (IL)-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) had much more potent BCA than complement C5a, leukotriene B4 and platelet activating factor, well known as granulocyte chemotactic factors. Chemotaxis rather than chemokinesis was shown in chequerboard analysis of basophil migration induced by IL-3 and GM-CSF. Relatively high concentrations of IL-5 also induced basophil migration, although predominantly chemokinetic. IL-8 had apparent BCA, which was not so high as that of C5a. In contrast, IL-2, IL-4, interferon(IFN)-gamma and granulocyte colony-stimulating factor (G-CSF) had no significant BCA. These findings suggest that IL-3, IL-5, GM-CSF and, perhaps, IL-8 have an effect on basophil migration as well as modulation of basophil mediator release and may provide some insight into the basophil accumulation observed in late-phase allergic responses.
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PMID:Effects of cytokines on human basophil chemotaxis. 133 81

The repertoire of cytokine and cytokine receptor mRNA expressed by unstimulated human thymocytes and thymic stromal cells was explored by a quantitative polymerase chain reaction (PCR) using sequence specific internal standards. Of the 18 cytokines tested we found a considerable overlap in the expression of cytokines by human thymocytes and by thymic stromal cells; both cell types express the mRNA for interleukin-1 beta(IL-1, IL-6, IL-7 and tumour necrosis factor-alpha (TNF-alpha). However, there are substantial differences in the levels of cytokine mRNA expressed in these two types of cells as revealed by the quantitative PCR assay. Stromal cells express considerably higher levels of IL-1 beta and IL-6 than thymocytes (14- and 27-fold respectively). In addition, a number of cytokines such as lymphotoxin and interferon-gamma (IFN-gamma), are expressed exclusively in thymocytes whereas others such as stem cell factor (SCF), IL-1 receptor antagonist-2 (IRAP-2) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are produced only in stromal cells. There is a complete overlap in the expression of a group of cytokine receptors tested in thymocytes and thymic stromal cells; these include IL-1R, IL-2R, IL-6R, IL-7R, TNFR and stem cell growth factor receptor (c-KIT). The expression of specific cytokines by thymic stromal cells and the parallel expression of their receptors on thymocytes under physiological conditions, support the hypothesis that these cytokines participate in paracrine interactions between these two cell populations during thymocyte differentiation.
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PMID:Expression of cytokines and their receptors by human thymocytes and thymic stromal cells. 133 59

Association of complement synthesis with cell differentiation in U937 cells was investigated using granulocyte-macrophage colony-stimulating factor (GM-CSF), vitamin D3 and interferon-gamma (IFN-gamma) as differentiation-inducing agents. GM-CSF or vitamin D3 enhanced the synthesis of the third component of complement (C3) by U937 cells, but had no stimulatory effect on the synthesis of the fourth component of complement (C4). IFN-gamma increased both C3 and C4 synthesis by U937 cells. Combination of two of these three agents resulted in synergistic enhancement and all three agents caused maximal enhancement of C3 synthesis. Vitamin D3 enhanced IFN-gamma-induced C4 synthesis by U937 cells. These results were confirmed by ELISA and SDS-PAGE after biosynthetic labelling. GM-CSF, vitamin D3 or IFN-gamma increased the expression of complement receptor type 3 (CR3), one of the markers of monocyte/macrophage differentiation. Two of these agents caused a further increase and all three agents maximal increase in CR3 expression. Since C3 was synthesized in parallel with the degree of CR3 expression, the synthesis of C3, but not C4, by U937 cells is thought to be closely related to cell differentiation. It was reconfirmed that the synthesis of C3 and C4 by U937 cells was independently regulated.
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PMID:Effects of cell differentiation on the synthesis of the third and fourth component of complement (C3, C4) by the human monocytic cell line U937. 133 36

We have studied the efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in stimulating haematopoiesis of patients with chemotherapy-induced myelosuppression. Ten patients with various myeloid and lymphoid neoplasias were treated daily with a single subcutaneous dose of rhGM-CSF (5 micrograms/kg/day), for a period of 5-10 days, after receiving highly myelotoxic chemotherapy. The treatment increased the white blood cell count (WBC) in nine of ten patients, primarily because of an increase in the number of neutrophils. Increase in bone marrow myeloid precursor cells, and myeloid to erythroid cell rations accompanied the white-cell response. In spite of this, five patients demonstrated rapid platelet recoveries, and in two patients erythrocyte levels increased after GM-CSF treatment. No toxicity was encountered with the cytokine therapy. Although rhGM-CSF was shown to stimulate haematopoiesis in patients with chemotherapy-induced myelosuppression, additional studies are needed to assess whether the use of GM-CSF will reduce chemotherapy-associated morbidity and improve response rates and survival among patients with neoplasias.
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PMID:Effect of recombinant human granulocyte-macrophage colony-stimulating factor on chemotherapy-induced myelosuppression. 134 Jan 91

Peripheral blood samples were collected from normal subjects and chronic viral hepatitis patients, and the in vitro capability of the peripheral blood mononuclear cells to produce various cytokine (interleukin-1 beta, interleukin-6, interferon-gamma, and granulocyte-macrophage colony-stimulating factor) were analyzed by adding pokeweed mitogen. We then investigated the effects of a herbal medicine "Sho-saiko-to" on the levels of cytokine production. The production levels of the 4 cytokines were significantly lower in the peripheral blood mononuclear cells of the patients (Patient Group) than in those of normal subjects (Control Group). The addition of Sho-saiko-to to the Patient Group resulted in improved productions of those cytokines, as well as an remarkable improvement of interleukin-1 beta production. The results demonstrated that Sho-saiko-to acts to improve such immunological abnormalities as decreased cytokine productions. Administration of Sho-saiko-to to chronic viral hepatitis patients is also expected to have immunological benefits.
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PMID:Efficacy of a herbal medicine "sho-saiko-to" on the improvement of impaired cytokine production of peripheral blood mononuclear cells in patients with chronic viral hepatitis. 134 May 7

We have previously shown that 3F8, a murine IgG3, monoclonal antibody (MoAb) specific for the ganglioside GD2, mediates tumor cell kill in vitro and in vivo. We now describe receptor requirements of polymorphonuclear leukocytes (PMN) in 3F8-mediated cytotoxicity (ADCC) of human GD2 (+) melanoma and neuroblastoma cell lines. PMN from a child with leukocyte adhesion deficiency (LAD) were devoid of CD11/CD18 adhesion molecules and mounted no detectable ADCC. MoAb to CD11b, CD11c, and CD18 each efficiently blocked ADCC by normal PMN. In contrast, a panel of different MoAbs to CD11a had no significant inhibitory effect on ADCC, a finding consistent with the low-to-absent expression of the CD11a ligand, intercellular adhesion molecule-1, on the target cells. Granulocyte-macrophage colony-stimulating factor (GM-CSF) significantly increased the expression of CD11b, CD11c, and CD18 on normal PMN, decreased the expression of Fc receptors (FcR), and enhanced ADCC by normal but not by LAD PMN. MoAbs to FcRII and FcRIII each efficiently blocked ADCC; anti-FcRI MoAb had no effect. Flow cytometry using anti-FcRII MoAb versus anti-FcRIII MoAb did not show cross competition, suggesting that inhibition of ADCC was not a steric effect resulting from FcRII proximity to FcRIII. PMN deficient in FcRIII (obtained from patients with paroxysmal nocturnal hemoglobinuria) and PMN depleted of FcRIII by treatment with elastase or phosphatidylinositol (PI)-specific phospholipase C produced low ADCC, supporting a role for the PI-liked FcRIII. Thus, optimal ADCC using human PMN, human solid tumor cells, and a clinically active MoAb (conditions that contrast with the heterologous antibodies and nonhuman or nonneoplastic targets used in most models of PMN ADCC) required CD11b, CD11c, FcRII, and the PI-linked FcRIII. Furthermore, in this clinically relevant system, GM-CSF enhancement of antitumor PMN ADCC correlated with increased expression of CD11/CD18 molecules.
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PMID:Absolute requirement of CD11/CD18 adhesion molecules, FcRII and the phosphatidylinositol-linked FcRIII for monoclonal antibody-mediated neutrophil antihuman tumor cytotoxicity. 134 7

The possibility that umbilical cord and placental blood from an HLA-identical sibling might produce stable donor-derived lymphohematopoietic engraftment was tested in a patient with juvenile chronic myelogenous leukemia (JCML). After conditioning with high-dose busulfan and cyclophosphamide, cryopreserved umbilical cord blood, containing 0.5 x 10(8) nucleated cells/kg and 2.7 x 10(4) colony forming units-granulocyte, macrophage (CFU-GM)/kg, was infused. A leukocyte count greater than 1,000/microL, absolute neutrophil count (ANC) greater than 500/microL, and platelet count greater than 20,000/microL (untransfused) were observed on days 39, 39, and 47 after transplantation, respectively. Donor cell engraftment was documented in the peripheral blood and bone marrow by cytogenetic analysis, restriction fragment length polymorphism (RFLP), and polymerase chain reaction (PCR) as early as day 21. Furthermore, the donor origin of each lymphohematopoietic lineage (ie, CD5+ T cells, CD19/20+ B cells, CFU-GM, and burst-forming unit-erythrocyte [BFU-E]) was confirmed. On day 200, assays of the peripheral blood and bone marrow showed an abnormal proliferation of CFU-GM at low seeding densities in the absence of exogenous growth factors, as well as a hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF), both pathophysiologic characteristics of JCML. Recurrent disease was confirmed histologically on day 225. Together, these results demonstrate that umbilical cord blood contains sufficient numbers of hematopoietic stem cells necessary for the engraftment of leukemia patients treated with myeloablative therapy and that the detection of "spontaneous" CFU-GM and hypersensitivity to GM-CSF after treatment is a marker of residual or recurrent disease in patients with JCML.
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PMID:Transplantation of umbilical cord blood after myeloablative therapy: analysis of engraftment. 152 Aug 88

High-dose therapy with autologous marrow support results in durable complete remissions in selected patients with relapsed lymphoma and leukemia who cannot be cured with conventional dose therapy. However, substantial morbidity and mortality result from the 3- to 6-week period of marrow aplasia until the reinfused marrow recovers adequate hematopoietic function. Hematopoietic growth factors, particularly used after chemotherapy, can increase the number of peripheral blood progenitor cells (PBPCs) present in systemic circulation. The reinfusion of PBPCs with marrow has recently been reported to reduce the time to recovery of adequate marrow function. This study was designed to determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF)-mobilized PBPCs alone (without marrow) would result in rapid and reliable hematopoietic reconstitution. Sixteen patients with metastatic breast cancer were treated with four cycles of doxorubicin, 5-fluorouracil, and methotrexate (AFM induction). Patients responding after the first two cycles were administered GM-CSF after the third and fourth cycles to recruit PBPCs for collection by two leukapheresis per cycle. These PBPCs were reinfused as the sole source of hematopoietic support after high doses of cyclophosphamide, thiotepa, and carboplatin. No marrow or hematopoietic cytokines were used after progenitor cell reinfusion. Granulocytes greater than or equal to 500/microL was observed on a median of day 14 (range, 8 to 57). Transfusion independence of platelets greater than or equal to 20,000/microL occurred on a median day of 12 (range, 8 to 134). However, three patients required the use of a reserve marrow for slow platelet engraftment. In retrospect, these patients were characterized by poor baseline bone marrow cellularity and poor platelet recovery after AFM induction therapy. When compared with 29 historical control patients who had received the same high-dose intensification chemotherapy using autologous marrow support, time to engraftment, antibiotic days, transfusion requirements, and lengths of hospital stay were all significantly improved for the patients receiving PBPCs. Thus, autologous PBPCs can be efficiently collected during mobilization by chemotherapy and GM-CSF and are an attractive alternative to marrow for hematopoietic support after high-dose therapy. The enhanced speed of recovery may reduce the morbidity, mortality, and cost of high-dose treatment. Furthermore, PBPC support may enhance the effectiveness of high-dose therapy by facilitating multiple courses of therapy.
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PMID:Mobilization of peripheral blood progenitor cells by chemotherapy and granulocyte-macrophage colony-stimulating factor for hematologic support after high-dose intensification for breast cancer. 135 Feb 29

Hematopoietic stem cells (HSC) transplanted in utero are in competition with endogenous HSC; thus, ultimately the graft constitutes a relatively small fraction of total HSC pool. To enhance the engraftment of donor cells in sheep fetuses, we preincubated these cells, ex vivo, for 16 hours at 37 degrees C with the conditioned medium from phytohemagglutinin-stimulated lymphocytes (PHA-LCM) before in utero transplantation. PHA-LCM is a rich source of hematopoietic growth factors in sheep. Subsequent engraftment was significantly higher in cells preincubated with PHA-LCM compared with fresh cells or those incubated with control medium only. This was reflected in all markers of the donor cells (hemoglobin type, karyotype, and progenitor cell assays). Brief ex vivo incubation with PHA-LCM also increased viability of all marrow cells as well as total numbers of progenitors. Similar enhancement of engraftment was also noted in monkeys after a brief preincubation of donor cells with interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF). We conclude that brief (16 hours) ex vivo incubation of donor cells with a source of such growth factors as IL-3 and GM-CSF enhances the subsequent engraftment of transplanted cells.
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PMID:Ex vivo incubation with growth factors enhances the engraftment of fetal hematopoietic cells transplanted in sheep fetuses. 135 Feb 30


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