Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied neutrophil functions (phagocytosis, intracellular killing and chemotaxis with or without recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and T cell functions (lymphocyte proliferation and production of GM-CSF in response to phytohemagglutin (PHA)) to clarify host defense mechanisms in the elderly. There was no significant difference in phagocytic activity of neutrophils between the elderly and control young adults. rhGM-CSF enhanced phagocytosis by neutrophils, and a similar degree of enhancement was obtained in both groups. Killing activity of neutrophils evaluated by the new Nitroblue tetrazolium reduction test in the elderly was significantly lower than that in young adults (p < 0.001), however, pretreatment of neutrophils with rhGM-CSF resulted in an increase of killing activity in the elderly, raising their response to a level comparable to that of young adults pretreated with rhGM-CSF. There was no significant difference between the elderly and young adults in chemotaxis of neutrophils. rhGM-CSF alone did not prime chemotaxis, but primed chemotaxis in response to chemoattractant (N-formyl-methionyl-leucyl-phenylalanin) in both individuals. Lymphocyte proliferation and production of GM-CSF in response to PHA in the elderly were significantly lower than those in the young adults (p < 0.001, p < 0.05, respectively). These results indicated that impaired T cell functions may contribute, at least in part, to susceptibility to bacterial infection in the elderly.
 ...
PMID:[Role of neutrophil and T cell functions in host defense mechanisms of the elderly]. 149 47

[3H]thymidine uptake by NFS-60 cells in microcultures was found to increase in a linear fashion with the increasing doses of purified recombinant human granulocyte colony-stimulating factor (rhG-CSF). Such increases were found neither with rhG-CSF samples pretreated with rabbit anti-rhG-CSF serum nor with other human colony-stimulating factors such as granulocyte-macrophage colony-stimulating factor (hGM-CSF) or macrophage colony-stimulating factor (hM-CSF). Based on these findings, sera from normal persons and patients with severe infections or various hematological disorders were tested after dialysis using this system in order to determine whether G-CSF levels in sera can be estimated or not. In ten normal persons, five patients with acute myelogenous leukemia (AML M1, M2, and M3), five with myelodysplastic syndrome, and four with chronic myelogenous leukemia, no increases in [3H]thymidine uptake were found within the dose range of 0.4 microliters to 50 microliters. In contrast, linear dose responses parallel to a G-CSF standard curve were observed in one patient with a severe bacterial infection, four with aplastic anemia, two with acute myelomonocytic leukemia (AMMoL) (M4), and two with idiopathic neutropenia tested. From the standard curve, the probable levels of G-CSF were calculated as follows: approximately 200 pg/ml with infection, 130-220 pg/ml with aplastic anemia, 150 and 200 pg/ml with AMMoL, and 1120 and 1200 pg/ml with idiopathic neutropenia. The activities of sera were reduced by the anti-rhG-CSF serum pretreatment in the same way as documented in the case of rhG-CSF. Furthermore, the level in a patient with a severe infection became undetectable soon after elimination of the infection and blood neutrophil counts had returned to normal. These findings indicate that the microbioassay system will be useful for measuring circulating G-CSF levels which would fluctuate in accord with requirements for stimulating neutrophil production or with abnormal production of hG-CSF.
 ...
PMID:A new bioassay for human granulocyte colony-stimulating factor (hG-CSF) using murine myeloblastic NFS-60 cells as targets and estimation of its levels in sera from normal healthy persons and patients with infectious and hematological disorders. 246 30

We have previously demonstrated that protein production and mRNA expression of granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and IL-3 are decreased in activated mononuclear cells (MNC) from human umbilical cord compared with adult peripheral blood. Reduced production of these colony-stimulating factors (CSF) during states of increased demand, as occurs during overwhelming bacterial infection, may play a role in the pathogenesis of neutropenia and thrombocytopenia in the newborn. To determine whether the reduced mRNA expression and CSF production from activated cord MNC is secondary to the decreased transcriptional activity of the corresponding genes, we determined the transcriptional rate of GM-CSF, G-CSF, IL-3, and M-CSF by nuclear run-on assays. Cord and adult MNC were isolated by Ficoll-Hypaque density centrifugation. A total of 10(8) MNC from cord and adult blood were stimulated as follows: GM-CSF and G-CSF [32 nmol/L phorbol-12-myristate-6-acetate (20 micrograms/L) + 2 mg/L phytohemagglutinin for 6 h]; IL-3 [32 nmol/L phorbol-12-myristate-6-acetate (20 micrograms/L) + 0.5 mumol/L A 23187 for 6 h]; and macrophage CSF (2 micrograms/L recombinant human GM-CSF for 24 h). The nuclei from unstimulated and stimulated cells were isolated and labeled with 32P-uridine triphosphate. Newly elongated 32P-labeled RNA transcripts were hybridized to slot blots of CSF DNA. To minimize cross hybridization artifacts, short fragments (0.5-1.0 kb) of cDNA were used.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Transcriptional rates of granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, interleukin-3, and macrophage colony-stimulating factor genes in activated cord versus adult mononuclear cells: alteration in cytokine expression may be secondary to posttranscriptional instability. 750 24

To investigate the physiological role of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the adaptation mechanisms of myelopoiesis to enhanced demand, we studied both cytokines and their myeloid target cells in hematologically healthy patients suffering from acute bacterial infections. Endogenous serum levels of G-CSF and GM-CSF, granulocyte-macrophage colony-forming cell (GM-CFC) concentrations, and differential counts were determined for the peripheral blood of 57 patients with clinically apparent bacterial infections (26 males and 31 females aged 16 to 89 years) and 18 healthy controls (8 males and 10 females aged 23 to 84 years). Patients were selected for acute-phase protein and at least two additional clinical signs reflecting a bacterial infection. Patients showed significantly higher numbers of myeloid progenitor cells than controls (median, 68 versus 26 GM-CFC/ml; P < or = 0.01). G-CSF but not GM-CSF levels were found to be elevated (> or = 50 to 863 pg/ml). In the acute stage of infection, progenitor and cytokine levels were not influenced by gender, differences in therapy, or localization of the infection. Progenitor and G-CSF levels were not associated with absolute neutrophil counts or C-reactive protein. However, a negative correlation between number of GM-CFC per milliliter and age (R = -0.47; P < or = 0.001) and an inverse relationship between the incidence of high GM-CFC concentrations and elevated G-CSF levels (phi = -0.34; P < or = 0.01) were found. Combining both parameters into a cytokine-progenitor pattern, we observed a highly significant age-dependent response of myelopoiesis to inflammation (P < or = 0.001). Younger patients had high progenitor counts (> 75 GM-CFC/ml) associated with G-CSF levels below 50 pg/ml, whereas for the older patients, the reverse pattern was predominant. The results indicate that the age-dependent myelopoietic response to acute bacterial infections is characterized by an inverse relationship between progenitor cells and G-CSF. The observed cytokine-progenitor patterns could have implications for therapy with G-CSF and the prognosis of infectious diseases.
 ...
PMID:Cytokines and progenitor cells of granulocytopoiesis in peripheral blood of patients with bacterial infections. 752 29

Serum levels of soluble intercellular adhesion molecule-1, soluble interleukin-2 receptor, and cytokines such as interleukin-3, interleukin-4, interleukin-6, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor were examined in patients with oral disorders with 20 healthy persons used as control subjects. Patients studied included 30 with squamous cell carcinoma, 26 with oral lichen planus, 20 with recurrent aphthous ulcer, 19 with acute odontogenic bacterial infection, 16 with pseudomembranous candidiasis, and 16 with herpetic gingivostomatitis. Compared with levels in control subjects, detectable serum levels of interleukin-3 (> or = 10 pg/ml) existed more frequently in pseudomembranous candidiasis (13/16), acute odontogenic bacterial infection (14/19), and squamous cell carcinoma (24/30) and of granulocyte-macrophage colony-stimulating factor (> or = 4 pg/ml) more frequently in recurrent aphthous ulcer (15/20) and squamous cell carcinoma (21/30). These cytokine levels were increased with T stage of squamous cell carcinoma. About 20 pg/ml of interleukin-4 was detected in serum from one third to one fourth of patients with oral lichen planus, recurrent aphthous ulcer, and squamous cell carcinoma. Tumor necrosis factor-alpha was hardly detected in most patients except those with oral lichen planus and squamous cell carcinoma in which about one third of the patients had more than 40 pg/ml of tumor necrosis factor-alpha in serum. More than 10 pg/ml of interleukin-6 was frequently detected in all disorders, especially recurrent aphthous ulcer (18/20), pseudomembranous candidiasis (12/16), and acute odontogenic bacterial infection (17/19).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Serum cytokines, interleukin-2 receptor, and soluble intercellular adhesion molecule-1 in oral disorders. 789 9

We provide a model for induction of T cell-independent, polysaccharide-specific Ig secretion in response to bacterial challenge. Two predominant pathways are defined that require the concerted action of multivalent membrane Ig cross-linking by the polysaccharide Ag with 1) various B cell-activating moieties contained within the bacterial pathogen and/or 2) cytokines, such as IFN-gamma and granulocyte-macrophage colony-stimulating factor produced by NK cells and macrophages, that become activated in a T cell-independent manner during bacterial infection.
 ...
PMID:A model for induction of T cell-independent humoral immunity in response to polysaccharide antigens. 880 17

T-cell receptor (TCR) alpha beta+ CD4- CD8- (double-negative; DN) T cells appear in the peritoneal cavity at an early stage of intraperitoneal (i.p.) infection with the intracellular pathogen Listeria monocytogenes. In the present report, we analysed the developmental pathway and functions of the TCR alpha beta+ DN T cells using the L. monocytogenes infection system. The TCR alpha beta+ DN T cells appeared in the peritoneal cavity after L. monocytogenes i.p. infection in adult-thymectomized lethally irradiated bone marrow chimeras and p56lck-deficient mice. The results demonstrated that the TCR alpha beta+ DN T cells can develop extrathymically in a p56lck-independent manner. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that the TCR alpha beta+ DN T cells expressed genes for interferon-gamma (IFN-gamma), the macrophage chemotactic factors MCP-1 and Eta-1, and granulocyte-macrophage colony-stimulating factor (GM-CSF) but lacked expression of genes for interleukin-2 (IL-2), IL-4 and IL-10. As expected from the RT-PCR analysis, the TCR alpha beta+ DN T cells produced IFN-gamma in response to anti-TCR beta monoclonal antibody (mAb), anti-CD3 mAb and L. monocytogenes-infected macrophages but IL-4 was undetectable after the stimulation. Furthermore, the intracellular cytokine staining analysis demonstrated that approximately half of the TCR alpha beta+ DN T cells detectable at the early stage of L. monocytogenes infection were IFN-gamma-producing cells. All of the results suggest that the TCR alpha beta+ DN T cells develop through a unique extrathymic p56lck-independent pathway and participate in early protection against bacterial infection through activation and accumulation of macrophages.
 ...
PMID:TCR alpha beta+ CD4- CD8- T cells differentiate extrathymically in an lck-independent manner and participate in early response against Listeria monocytogenes infection through interferon-gamma production. 937 88

A variety of approaches to antitumor therapy are currently being explored that use both antigen-encoding DNA and noncoding nucleotides as a component of gene vaccination. Among the specific strategies reviewed are a construct that fuses a single-chain variable fragment (scFv) that incorporates both the variable-region genes necessary to encode the idiotypic determinants with fragment C (FrC) of tetanus toxin; a novel vector system using herpes simplex virus 1 (HSV-1) for in vivo gene delivery; the possibility of eliciting hyperacute xenograft response to treat human cancer; and the use of gene gun-mediated granulocyte-macrophage colony-stimulating factor (GM-CSF) cDNA-based tumor cell vaccines. The protection provided by DNA vaccination against viral diseases such as influenza suggested a role for such vaccines against cancer. However, unlike vaccines against infectious diseases, cancer vaccines are therapeutic, rather than prophylactic. With multiple myeloma, for example, it is possible that the optimal timing of administration of such a vaccine is during a remission that has been induced by traditional therapies, to eliminate residual disease. DNA cancer vaccines are designed to activate immune responses to tumor antigens to which the immune system has already been exposed. To do so, the vaccines must first overcome immune tolerance that may have already developed to the tumor. There is increasing evidence that tumor antigens, unlike viral or bacterial antigens, do not consistently activate an immune response. One major factor in determining whether a reaction occurs appears to be whether antigen presentation is accompanied by danger signals. With viral or bacterial infection, the accompanying tissue destruction and inflammation produce costimulatory signals that promote T-cell activation. However, inflammatory and tissue-destructive processes are absent during initial tumor transformation. The typical outcome may be immunologic tolerance.
 ...
PMID:DNA vaccination against multiple myeloma. 998 89

Neutropenia frequently complicates infection due to human immunodeficiency virus (HIV). The etiology of neutropenia in this setting includes bone marrow infection or infiltration, myelosuppressive therapies, the presence of antibodies to HIV, and accelerated apoptosis. Protection against microbial invaders by neutrophils is further compromised by impaired chemotaxis and phagocytosis, production of toxic oxygen species, and expression of cellular adhesion molecules. Neutropenia is a significant risk factor for bacterial infection in HIV-infected patients. Endogenous cytokines, such as granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor, regulate neutrophil count and function. Treatment with recombinant human methionyl G-CSF (filgrastim) has lessened neutropenia in patients with HIV infection. Clinical trials have shown that the incidence of bacterial infections and the number of consequent days of hospitalization for HIV-infected patients receiving filgrastim therapy are lower. Filgrastim treatment also allows administration of larger doses of myelosuppressive agents.
 ...
PMID:Neutropenia, neutrophil dysfunction, and bacterial infection in patients with human immunodeficiency virus disease: the role of granulocyte colony-stimulating factor. 1067 24

Mast cells are important as sentinel cells in host defense against bacterial infection. Much of their effectiveness depends upon recruiting other immune cells; however, little is known about the mechanisms of this response. CCL20, also known as macrophage inflammatory protein-3alpha (MIP-3alpha), Exodus, and LARC, is a chemokine known to be a potent chemoattractant for immature dendritic cells and T cells. In this study, we examined the human mast cell production of both CCL20 and granulocyte-macrophage colony-stimulating factor (GM-CSF), a critical cytokine for innate immune responses in the lung, in response to Pseudomonas aeruginosa. Reverse transcription-PCR and Western blot analysis demonstrated that the human mast cells (HMC-1) express CCL20 mRNA and are able to produce a significant amount (32.4 ng/ml) of CCL20 protein following stimulation by calcium ionophore and phorbol myristate acetate. Importantly, P. aeruginosa potently stimulated CCL20 production in human cord blood-derived mast cells (CBMC), with production peaking at 6 h after stimulation. This time course of expression was distinct from that of GM-CSF, which peaked after 24 to 48 h. Significant CCL20 production did not occur following immunoglobulin E-mediated activation of CBMC under conditions which induced a substantial GM-CSF response. Interestingly, the CCL20 response of mast cells to P. aeruginosa was relatively resistant to inhibition by the corticosteroid dexamethasone, interleukin-10, or cyclosporine, while GM-CSF production was potently inhibited. However, P. aeruginosa-induced CCL20 production was blocked by the protein kinase C (PKC) inhibitor Ro 31-8220 and a PKC pseudosubstrate. These results support a role for human mast cells in the initiation of immune responses to P. aeruginosa infection.
 ...
PMID:Selective early production of CCL20, or macrophage inflammatory protein 3alpha, by human mast cells in response to Pseudomonas aeruginosa. 1249 86


1 2 3 Next >>