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)

Mast cells are important effector cells in IgE-mediated acute allergic reactions. Mast cells also produce cytokines such as interleukin (IL)-3, IL-4, IL-5, tumor necrosis factor (TNF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) that regulate the function of eosinophils and the development of a late-phase inflammatory response to antigen challenge. To evaluate the role of mast cells on the development of IgE-mediated allergic pulmonary eosinophilia in vivo, we compared the eosinophil infiltration into lungs of mast cell deficient mice (WBB6F1/J-W/Wv) with their congenic normal littermates (W/W+). Mice were sensitized with alum-precipitated ovalbumin and challenged with aerosolized ovalbumin on day 12 after sensitization. Bronchoalveolar lavage (BAL) fluid, lung tissue biopsies, and blood samples were collected after ovalbumin challenge. Eosinophil numbers in the BAL and lung tissue, lung eosinophil peroxidase (EPO) activity and serum levels of IgE and IgG1 were measured. In sensitized W/W+ mice, there were increased numbers of eosinophils in the BAL fluid and lung tissue, and EPO levels were increased after ovalbumin challenge. Ovalbumin challenge of sensitized mast-cell-deficient mice produced fewer numbers of eosinophils in the BAL fluid and lungs, and EPO levels were also reduced compared with their challenged congenic littermates. On the other hand, levels of serum IgE and IgG1 were not different between W/Wv mice and their congenic littermates.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mast cells modulate allergic pulmonary eosinophilia in mice. 769 19

In order to obtain the beneficial effects from granulocyte-macrophage colony-stimulating factor (GM-CSF) on granulo-monocyte recovery with the minimum dose and toxicity, we compared the effect of two different GM-CSF schedules (5 micrograms/kg/day subcutaneously, days 5 to > 18 versus days 12 to > 18 on the cytopenias which follow cytostatic treatment with carboplatin (400 mg/m2 intravenous (i.v.) day 1) and etoposide (100 mg/m2 i.v. days 1 to > 3). 13 patients entered the study for a total of 36 evaluable cycles. The cytostatic treatment produced a neutropenia that persisted for up to day 22 (absolute neutrophil count (ANC) < 1000/microliters in 25% and ANC < 2000 in 50% of control cycles). Early GM-CSF administration markedly increased the leucocyte nadir and produced two waves of leucocytosis: an early one, linked to marrow reserve release and presumably of no value to the patients; and a delayed one, due to marrow precursor and progenitor cell proliferation, in which the granulomonocytosis was associated with a marked eosinophilia. The delayed GM-CSF administration markedly increased the leucocyte nadir and accelerated granulo-monocyte recovery (with an only modest eosinophilia), so that chemotherapy could be repeated every 21 days in all the patients.
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PMID:A comparison of two GM-CSF schedules to counteract the granulo-monocytopenia of carboplatin-etoposide chemotherapy. 769 78

Transcriptional regulation of the interleukin-5 (IL-5) gene in T lymphocytes appears to be of central importance in the control of the eosinophilia characteristic of allergic responses and certain parasite infections. Previous studies of IL-5 gene regulation have been hampered by the lack of a transfection assay, which detects the antigen-responsive enhancer in the IL-5 promoter. Here we show that stable transfection of the Th2 clone D10.G4.1 and the T lymphoma EL4.23 with chloramphenicol acetyltransferase reporter gene constructs carrying the region to -3859 gives inducible expression with the known regulatory characteristics of the endogenous IL-5 gene. To facilitate detailed analysis of the promoter region, 3.9 kb of DNA sequence immediately up stream of the start of transcription was determined and the minimum upstream region required for inducible expression was further localized, by stable transfection studies in EL4.23 cells, to the region up to -1016. A CTF/NF1 site in the upstream enhancer at -940 to -928 was shown to be required for regulated inducible expression. Mutation of this sequence motif abolished inducibility and also prevented binding of the sequence to a nuclear protein(s). A TCATTT-containing element in the proximal promoter region was also demonstrated to be essential for inducible expression of the IL-5 gene, similar to the role of this conserved element in the transcriptional regulation of the granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4 genes.
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PMID:Localization of the inducible enhancer in the mouse interleukin-5 gene that is responsive to T-cell receptor stimulation. 771 77

This study was undertaken to test the hypothesis that the combination of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-alpha-2b (INF-alpha) would have a favorable clinical impact on patients with advanced renal cell carcinoma. Fifteen patients were treated with INF-alpha, 5 million U/m2 three times a week and GM-CSF 5 micrograms/kg, subcutaneously, daily. Patients received two consecutive 4-week cycles and then restaged. There were no complete responses, two of 15 partial responses (13%), and 13 of 15 had no response (87%). Biological effects (eosinophilia and leukocytosis) were characteristically observed. The therapy was well tolerated, and most side effects were attributable to INF-alpha. The study failed to show that the addition of GM-CSF to INF-alpha would increase the response rate in patients with metastatic renal cell carcinoma by enhancement of macrophage tumoricidal activity.
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PMID:A phase II trial of concomitant interferon-alpha-2b and granulocyte-macrophage colony-stimulating factor in patients with advanced renal cell carcinoma. 772 6

Mechanisms of eosinophilia were compared between in vitro bone marrow cell cultures of congenitally athymic (nu/nu) mice and their heterozygous littermates (nu/+). Cultures of 5 x 10(4) bone marrow cells using interleukin 3 (IL-3), IL-5 and granulocyte-macrophage colony-stimulating factor showed that nu/nu and nu/+ mice mimicked each other in eosinophil production both before and after infection with Toxocara canis. Eosinophil differentiating activity (EDA) was detected in media conditioned by spleen cells and lungs of T. canis infected nu/+ mice, although nu/nu mice showed EDA only in lung-conditioned medium. EDA, detected both in infected nu/nu and nu/+ mice, was inhibited by an anti-IL-5 monoclonal antibody. These results indicate that IL-5 may be produced by lung cells of both nu/nu and nu/+ mice as well as by spleen cells of nu/+ mice infected with T. canis, which is the reason why nu/nu mice infected with T. canis exhibit blood eosinophilia.
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PMID:Mechanisms of eosinophilia in Toxocara canis infected mice: in vitro production of interleukin 5 by lung cells of both normal and congenitally athymic nude mice. 787 46

This study evaluated immunoreactivity for several cytokines in bronchial tissue of asthmatic patients and related this to the clinical and functional characteristics. Patients were allocated into two different groups on the basis of their atopic status (atopic and nonatopic), with two subgroups of symptomatic and asymptomatic subjects in each. Five healthy volunteers were tested as control subjects. After clinical and functional assessment, all of the subjects underwent bronchoscopy. Several biopsy specimens were obtained for immunohistochemical and immunoelectron microscopic evaluation. Symptomatic asthmatic subjects had increased expression of immunoreactive interleukin (IL) 1 beta, IL-2, IL-3, IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor alpha (TNF alpha) when compared to the asymptomatic patients or normal control subjects. The cell sources of IL-1 beta were monocytes and dendritic cells in atopic patients and monocytes alone in nonatopic asthmatic subjects. The CD4+ T lymphocytes from atopic asthmatic subjects predominantly expressed IL-3, IL-4, IL-5, and GM-CSF immunoreactivity, whereas CD4+ T cells from nonatopic patients predominantly expressed IL-2, IL-3, and IL-5, and GM-CSF immunoreactivity. Mast cells showed immunoreactivity for TNF alpha, IL-3, IL-5, and GM-CSF. Immunostaining for TNF alpha and GM-CSF was also detected in bronchial epithelial cells and monocytes. Tissue eosinophilia and the level of airway hyperresponsiveness more closely correlated with IL-5 immunoreactivity in atopic asthmatic subjects and with IL-2 and GM-CSF immunoreactivity in nonatopic patients.
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PMID:Detection of cytokines and their cell sources in bronchial biopsy specimens from asthmatic patients. Relationship to atopic status, symptoms, and level of airway hyperresponsiveness. 813 26

A case of non-Hodgkin's T cell lymphoma (diffuse lymphoma, large cell type) associated with marked eosinophilia and pleurisy in a 57-year-old male is reported. The leukocyte count was 12.5 x 10(3)/microliters and eosinophil count was 53% and the absolute count of 6.6 x 10(3)/microliters. The patient's serum and pleural effusion fluid, containing abundant lymphoma cells, showed eosinophil colony stimulating factor (Eo-CSF) activity. Conditioned medium (CM) prepared from patient's T cells (T-CM) produced Eo-CSF and this was enhanced by interleukin-2 (IL-2) stimulation. We demonstrated that the patient's serum contained a significant amount of interleukin-5 (IL-5) and the patient's T-CM, particularly after IL-2 stimulation contained a significant amount of granulocyte-macrophage colony-stimulating factor (GM-CSF). These findings suggest that Eo-CSF produced by neoplastic T cells or normal T cells activated by tumor antigen stimulated the production of eosinophils in this patient and that both IL-5 and GM-CSF might play a role in Eo-CSF activity.
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PMID:[Non-Hodgkin's T cell lymphoma associated with marked eosinophilia]. 823 Jul 43

In previous research, we have observed that intrathoracic administration of platelet-activating factor-acether (PAF) promoted a delayed eosinophilia in the pleural cavity of rats that lasted for at least 96 h. We investigated the ability of pleural washings from rats previously injected with PAF (1 micrograms/cavity) to stimulate in vitro murine hematopoietic eosinophil proliferation. We observed that pleural fluid sustained eosinophil proliferation but not differentiation, under conditions in which PAF itself had no effect. The phenomenon lasted for 3 days and was maximal on the 1st day of culture. Treatment with neutralizing antibodies against interleukin (IL)-5, granulocyte-macrophage colony-stimulating factor (GM-CSF) or IL-3, alone or in combination, did not modify the eosinophil proliferation induced by PAF pleural fluid, suggesting that these cytokines may not be involved in the studied phenomenon. We conclude that the rat pleural fluid obtained 6 h after PAF administration induces eosinophil proliferation in vitro by a mechanism probably independent of IL-5, GM-CSF or IL-3.
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PMID:Eosinophil granulocyte proliferation induced by an intermediate factor generated in the pleural cavity of rats injected with platelet-activating factor-acether. 824 99

Cytogenetic analysis of bone marrow (BM) cells from a patient with myelodysplastic syndrome (MDS) associated with eosinophilia showed a 45,XY,t(12;21)(q23;q22), -17 karyotype. We performed clonal and suspension cultures using the patient's BM mononuclear cells to clarify the mechanism of eosinophilia. Eosinophil colonies formed in the presence of interleukin-5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF), but not in the presence of IL-3. When BM cells were cultured in suspension in the presence of IL-5, they differentiated to mature eosinophils, and chromosome analysis identified the 45,XY,t(12;21)(q23;q22), -17 karyotype in all metaphases. The patient's serum did not stimulate eosinophil proliferation or differentiation in comparison with normal serum, however, these data suggest that the abnormal clone with 45,XY,t(12;21)(q23;q22), -17 karyotype may have an increased responsiveness to IL-5 and GM-CSF, resulting in eosinophilia.
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PMID:Eosinophilia in myelodysplastic syndrome with a (12;21)(q23;q22) translocation. 835 11

The relative contributions of type 1 and 2 T-helper (Th1 and Th2) cell-derived interleukin (IL-5), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-3 were studied in the regulation of sequential events in the development of eosinophilia. Using eosinophils from normal donors and neutralizing antibodies that selectively block cytokine activities, we analyzed the effects of these cytokines in supernatants (SN) of well-characterized allergen-specific Th2 and Th1 T-lymphocyte clones (TLC) generated from atopic and nonatopic individuals, respectively. Eosinophil colony formation from CD34+ bone marrow progenitor cells in semisolid cultures could be induced both by Th1 and Th2 SN, mainly mediated by the synergistic effects of GM-CSF and IL-3, whereas IL-5 had only a minor additive effect. High production of mature eosinophils in liquid cultures of unseparated mononuclear bone marrow cells could only be induced by Th2 SN, which could be more than 90% blocked by anti-IL-5, but not by anti-IL-3 or anti-GM-CSF. Chemotaxis of mature peripheral blood eosinophils could equally well be induced by Th1 and Th2 SN, although the relative contribution of the individual cytokines was clearly different in the two sets of SN. Priming of platelet-activating factor (PAF) release by peripheral blood eosinophils was regulated by additive effects of the three cytokines and was stronger induced by the Th2 SN than by the Th1 SN. The present results indicate that IL-5, GM-CSF, and IL-3 control eosinophils throughout the course of development of eosinophilia, having different individual contributions in different compartments. The apparent strong and selective IL-5-dependence of certain yet undefined steps in eosinophil production in the bone marrow supports the concept of the generally assumed causal relation between predominant activation of IL-5-producing Th2 cells in response to allergens and development of eosinophilia in atopic disease.
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PMID:Relative contributions of human types 1 and 2 T-helper cell-derived eosinophilotrophic cytokines to development of eosinophilia. 836 99


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