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)

Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates production of neutrophils in bone marrow and may decrease the incidence of infection during neutropenia. We evaluated the protective role of recombinant GM-CSF against Pseudomonas aeruginosa challenge in neutropenic mice. CD-1 mice treated with cyclophosphamide on days 1 and 2 of the experiment were given GM-CSF (1, 2, or 4 micrograms/day) starting at day 4 of the experiment according to the following protocol: 1) 1 microgram of GM-CSF 2 hr and 24 hr after challenge; 2) 1 microgram 24 hr before challenge, 2 hr and 24 hr after challenge; 3) 2 micrograms injected 24 hr before and 2 hr after challenge; 4) 2 micrograms given 24 hr before and 2 micrograms given 2 hr and 24 hr after challenge; 5) 4 micrograms administered 2 hr and 24 hr after challenge; and 6) saline and bovine albumin controls. The number of blood neutrophils by days 4 and 5 was similar for GM-CSF-treated and untreated animals. Survival was significantly greater in animals given 2 micrograms of GM-CSF at 24 hr before and at 2 hr and 24 hr after challenge with Pseudomonas. Neutrophils and splenic macrophages obtained from GM-CSF-treated mice (2 micrograms/animal) produced significantly greater amounts of O2- (204 +/- 36 nmoles/10(5) cells) than controls (21 +/- 10 nmoles/10(5) cells). Additionally, neutrophils and macrophages from GM-CSF-treated mice killed significantly more bacteria (P. aeruginosa) in vitro and had a greater number of C3b and Fc receptors (78 +/- 12% and 89 +/- 8%) than did cells obtained from control animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protection against gram-negative bacteremia in neutropenic mice with recombinant granulocyte-macrophage colony-stimulating factor. 196 50

The ability of recombinant murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF) to protect myelosuppressed mice against lethal infections was evaluated. In mice myelosuppressed by cyclophosphamide, subcutaneously administered rmGM-CSF was a potent stimulus of granulopoiesis by increasing the number of GM-CSF-responsive precursor cells in bone marrow followed by a profound neutrophilia. Neutrophil recovery was augmented by rmGM-CSF in a dose-dependent manner at daily doses of 0.6-5.0 micrograms/mouse. In addition, rmGM-CSF increased the functional activity of circulating neutrophils at similar doses. When rmGM-CSF was administered to neutropenic mice before experimentally induced Pseudomonas aeruginosa, Staphylococcus aureus, or Candida albicans infections, it protected against these lethal infections, resulting in increased numbers of survivors. These data suggest that rmGM-CSF protects neutropenic mice from lethal infections, probably by augmenting neutrophil recovery after myelosuppression and activation of mature cells.
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PMID:Recombinant murine granulocyte-macrophage colony-stimulating factor augments neutrophil recovery and enhances resistance to infections in myelosuppressed mice. 199 31

The effects of recombinant murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF) against Pseudomonas aeruginosa infection in ICR mice were investigated. Mice were treated with cyclophosphamide (CPA) and were then injected intraperitoneally with rmGM-CSF three times daily, beginning on the day after CPA treatment, for 7 days. The number of peripheral blood leukocytes in both CPA- and rmGM-CSF-treated mice and control CPA-treated mice reached a nadir on day 4, when P. aeruginosa was injected intraperitoneally. The administration of rmGM-CSF significantly increased the proportion of survivors among mice infected with a lethal dose of P. aeruginosa. This effect was further analyzed by monitoring sequential changes in leukocyte count and bacterial growth in various organs. The number of bacteria in the peritoneal cavities, peripheral blood samples, and livers of GM-CSF-treated mice decreased to an undetectable level after a transient increase, and the number was significantly lower than that in control mice. In GM-CSF-treated mice, the neutrophil levels in peripheral blood started to increase 5 days after CPA administration and were consistently higher than those in controls. Furthermore, the neutrophils in GM-CSF-treated mice were more mature morphologically. Thus, the prophylactic effect of rmGM-CSF against P. aeruginosa infection may result from a rapid recovery of myelopoiesis and a partial enhancement of mature neutrophil function.
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PMID:Protective effect of recombinant murine granulocyte-macrophage colony-stimulating factor against Pseudomonas aeruginosa infection in leukocytopenic mice. 265 23

Previous studies have demonstrated that Pseudomonas exotoxin A stimulated the proliferation of immature T lymphocytes within the splenocytes of athymic mice. These studies were performed to determine which lymphokines were involved in the proliferation of the immature T cells. The results of this study indicate that exotoxin A does not induce the production of interleukin-2 or tumor necrosis factor from B cell-depleted splenotypes from athymic mice. However, exotoxin A does induce the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) from B cell-depleted splenocytes. Furthermore, the GM-CSF was shown to be produced by a Thy1+, CD4-, CD8- T lymphocyte. The addition of anti-GM-CSF antibody abrogates the exotoxin A-induced proliferation of B cell-depleted splenocytes from athymic mice. Thus, these data indicate that exotoxin A induces the production of GM-CSF from immature T lymphocytes within the splenocytes of athymic mice and the exotoxin A-induced proliferation of these immature T cells is dependent on the presence of GM-CSF.
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PMID:GM-CSF is required for the Pseudomonas exotoxin A-induced proliferation of immature T cells in athymic mice. 784 87

Infections remain a serious problem following injury. Immune modulation offers an additional strategy for the treatment of infections. We evaluated the ability of a multilineage hematopoietic growth factor, granulocyte-macrophage colony-stimulating factor (GM-CSF), to improve survival following burn injury with a superimposed burn wound infection. Groups of 12 BDF1 mice received a 15% total body surface area (TBSA) thermal injury by immersion in 100 degrees C water; 6 x 10(3) Pseudomonas was then applied to the burn wound. The GM-CSF was injected subcutaneously B.I.D. for 7 days. Mice receiving the 10-ng dose of GM-CSF had significantly improved survival compared with the controls; other doses had no significant effect on survival. Clinical trials to assess the ability of GM-CSF to reduce infectious complications following burn injury are underway and these data suggest selecting a specific dose may be critical in achieving maximal benefit.
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PMID:Dose dependency of granulocyte-macrophage colony stimulating factor for improving survival following burn wound infection. 815 7

Treatment with a single low dose (80 to 800 ng) of interleukin-1 (IL-1) 24 h before a lethal bacterial challenge in granulocytopenic and in normal mice enhances nonspecific resistance. The mechanism behind this protection has only partially been elucidated. Since IL-1 induces production of tumor necrosis factor alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), platelet-activating factor (PAF), and arachidonic acid metabolites, we investigated the potential role of these substances in IL-1-induced protection. Low doses of murine TNF-alpha but not of human TNF-alpha enhanced survival, suggesting an effect via the type II TNF receptor rather than the type I TNF receptor, which has little species specificity. In line with this TNF-alpha-induced protection from infection, pretreatment with a low dose of a rat anti-murine TNF-alpha monoclonal antibody tended to inhibit IL-1-induced protection, suggesting a role of TNF-alpha as a mediator of IL-1-induced enhanced resistance to infection. Pretreatment with higher doses of anti-TNF-alpha, however, showed a dose-related protective effect per se, which could be further enhanced by a suboptimal dose of IL-1. A combination of optimal doses of anti-TNF-alpha and IL-1 produced an increase in survival similar to that produced by separate pretreatments. This lack of further enhancement of survival by combined optimal pretreatments suggests a similar mechanism of protection, most likely attenuation of deleterious effects of overproduced proinflammatory cytokines like TNF-alpha during lethal infection. Pretreatment with different doses of GM-CSF before a lethal Pseudomonas aeruginosa challenge in neutropenic mice did not enhance survival. Different doses of WEB 2170, a selective PAF receptor antagonist, of MK-886, a selective inhibitor of leukotriene biosynthesis, or of several cyclooxygenase inhibitors did not reduce the protective effect of IL-1 pretreatment. We conclude that IL-1-induced nonspecific resistance is partially mediated by induction of TNF-alpha and not by GM-CSF, PAF, and arachidonic acid metabolites. The mechanism of action of IL-1 seems to be similar to that of anti-TNF-alpha.
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PMID:Roles of tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, platelet-activating factor, and arachidonic acid metabolites in interleukin-1-induced resistance to infection in neutropenic mice. 816 71

The effects of indomethacin administration on Pseudomonas aeruginosa infection were investigated in neutropenic mice. Cyclophosphamide-treated mice received the drug at 2.5 to 12 mg/kg according to different regimens, to be challenged with a lethal intraperitoneal inoculum of P. aeruginosa 5 days after myelosuppression. A single exposure of the neutropenic mice to 7 mg/kg indomethacin during the first 6 to 48 hr after myelosuppression was found to optimally restore the animals' antibacterial resistance, both in terms of survival of infected mice and clearance of the organisms from the peritoneal cavity. However, when administered 24 hr before challenge, the same drug dosage had no effect in enhancing survival. Cure was associated with accelerated hematopoietic recovery, as revealed by peripheral blood leukocyte counts, spleen weight and cellularity, cellular response to infection in the peritoneal cavity, and enumeration in vitro of bone marrow and splenic granulocyte-macrophage colony-forming cells. Following indomethacin administration, a rapid burst in the levels of colony-stimulating activity was detected in the bloodstream, and exposure of splenic macrophages or marrow cells to indomethacin in vitro was found to result in enhanced expression of transcripts specific for granulocyte-macrophage colony-stimulating factor. These data support the notion that the administration of cyclooxygenase inhibitors may be useful in promoting hematopoiesis and reducing the risk of opportunistic infections in myelosuppressed hosts.
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PMID:Accelerated hematopoietic recovery and protective effect of the cyclooxygenase inhibitor indomethacin in bacterial infection of neutropenic mice. 845 76

Using a multiprobe RNase protection assay, we examined cytokine and chemokine mRNAs that were expressed after corneal infection with Pseudomonas aeruginosa in mice. Cytokines that were upregulated included interleukin-1alpha (IL-1alpha) and -1beta, IL-1 receptor antagonist, IL-6, IL-11, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, stem cell factor, lymphotoxin beta, transforming growth factor beta1, and tumor necrosis factor alpha. Chemokine transcripts that were upregulated included Eotaxin; gamma-interferon-inducible protein 10; monocyte chemoattractant protein 1; macrophage inflammatory proteins 1alpha, 1beta, and 2; and RANTES. Peak expression of these cytokines and chemokines was observed between 1 and 3 days after infection. These responses returned to or approached baseline preinfection levels by 7 days after ocular challenge. Identification of the various cytokines and chemokines upregulated during corneal infection provides important information relevant to unraveling the pathogenesis induced by this bacterium and provides hope that specific molecules can be targeted for therapy.
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PMID:Early cytokine and chemokine gene expression during Pseudomonas aeruginosa corneal infection in mice. 942 85

The finding of outer membrane protein I (OprI) of Pseudomonas aeruginosa in hemodialyzers used by patients with end-stage renal failure led us to study the possible role of OprI as cytokine inducer. However, there are few reports on the biological activity of OprI, because it is difficult to obtain highly purified OprI. In this study, we attempt to establish a procedure for the efficient purification of OprI, which does not include lipopolysaccharide, from the bacterial culture broth, not hemodialyzers, to demonstrate that OprI is a potent cytokine inducer. From bacterial culture broth (1 liter), P. aeruginosa PAO1, which was confirmed previously by the sequence coding, was separated by centrifugation, high-performance liquid chromatography, and disk electrophoresis. Mouse bone marrow cells were stimulated by purified OprI, and the supernatants of the culture were analyzed by several enzyme-linked immunosorbent assay kits. The tumor necrosis factor alpha production stimulated by purified OprI was confirmed and degraded within 24 h. Furthermore, interleukin (IL) 1alpha, IL-1beta, IL-6, and granulocyte-macrophage colony-stimulating factor were also induced by OprI despite the absence of lipopolysaccharide. We conclude that OprI has the potential to induce tumor necrosis factor alpha production in mouse bone marrow cells and that tumor necrosis factor alpha contributes to the induction of inflammatory cytokines, namely IL-1alpha, IL-1beta, IL-6, and granulocyte/macrophage colony-stimulating factor, while lipopolysaccharide has little effect on these cells. These results suggest the presence of a pathway of inflammatory signal transduction triggered by OprI. In addition, OprI is possibly one of the harmful dialysate pollutants in hemodialysis patients besides the well-known lipopolysaccharide.
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PMID:The outer membrane protein I of Pseudomonas aeruginosa PAO1, a possible pollutant of dialysate in hemodialysis, induces cytokines in mouse bone marrow cells. 1045 34

Although the cytotoxicity of lipopolysaccharide (LPS) derived from Pseudomonas aeruginosa, i.e. Limulus amoebocyte lysate activity, is less potent than that from Escherichia coli 0127:B8, P. aeruginosa induces prominent sustained lung inflammation, as in cystic fibrosis. The present study was designed to examine the potential for several LPSs obtained from E. coli and P. aeruginosa to release monocyte chemotactic activity (MCA) from lung cells. LPSs differentially stimulated A549 cells, BEAS-2B cells and lung fibroblasts to release MCA (P. aeruginosa >E. coli 0127:B8 from Difco >055:B5 from Sigma >026:B6 (Sigma)). E. coli 0127:B8 (Sigma) and 0111:B4 (Sigma) did not stimulate these cells. MCA was determined by means of checkerboard analysis. Molecular sieve column chromatography revealed four chemotactic peaks. The release of MCA was inhibited by cycloheximide and lipoxygenase inhibitors. Experiments with blocking antibodies suggested that much of the MCA was secondary to monocyte chemoattractant protein-1 (MCP-1) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Thus, the concentrations of these chemoattractants were examined and it was found that the potency of the various LPSs to stimulate MCA closely paralleled their potency in releasing MCP-1 and GM-GSF. Serum augmented the release of MCP-1 and GM-CSF. However, the differences among LPSs from E. coli and P. aeruginosa in stimulating A549 cells were observed. These data suggest that Pseudomonas aeruginosa lipopolysaccharide may stimulate lung cells to release more monocyte chemotactic activity than lipopolysaccharides derived from Escherichia coli, leading to sustained prominent lung inflammation.
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PMID:The potential of various lipopolysaccharides to release monocyte chemotactic activity from lung epithelial cells and fibroblasts. 1054 73


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