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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)

Infection of mice with Plasmodium berghei engendered a temporary appearance of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the serum. The peak of GM-CSF levels was detected at day 2 post-infection, and then gradually decreased. On the other hand, the number of committed stem cells for granulocytes and macrophages (CFU-GM) in bone marrow transiently decreased at day 2 post-infection, and then increased and peaked at day 6 post-infection. When the serum of P. berghei-infected mice was fractionated by gel chromatography on Sephacryl S-300, GM-CSF activity was detected as a single peak with an apparent molecular weight of 64 KDa. GM-CSF was entirely adsorbed to concanavalin A-Sepharose 4B affinity chromatography, and was sensitive to pronase digestion, indicating its glycoprotein nature. These results suggest that the circulating GM-CSF would contribute the increase of granulocyte-macrophage hemopoiesis in the early phase of malaria.
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PMID:Temporary appearance of a circulating granulocyte-macrophage colony-stimulating factor in lethal murine malaria. 918 64

The production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by lymphocytes was examined in murine malaria. When spleen cells or lymph node cells from P. berghei-infected mice were cultured in vitro with malaria antigen, the GM-CSF production correlated with the incubation time up to 72 hours. When lymphocytes obtained at various days after infection were cultured with the antigen, GM-CSF became detectable as early as 2 days after infection, reached a peak at day 9 and then rapidly decreased. Production of GM-CSF was antigen-specific, and related to the dose of antigen. Treatment of lymphocytes with anti-Thy-1.2 antibody and complement resulted in almost complete loss of GM-CSF-producing activity, while treatment with either anti-CD4 or anti-CD8 antibody and complement resulted in partial loss of GM-CSF-producing activity, indicating that both CD4+ and CD8+ T cells are involved in GM-CSF production in malaria. GM-CSF exhibits glycoprotein nature, and has an apparent molecular weight of 36,000. The molecular properties of this T-cell derived GM-CSF were compared with those of known lymphokine GM-CSF.
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PMID:Granulocyte-macrophage colony-stimulating factor production by T lymphocytes in Plasmodium berghei-infected mice. 965 99

Using the murine parasite Plasmodium yoelii (Py) as a model for malaria vaccine development, we have previously shown that a DNA plasmid encoding the Py circumsporozoite protein (PyCSP) can protect mice against sporozoite infection. We now report that mixing a new plasmid PyCSP1012 with a plasmid encoding murine granulocyte-macrophage colony-stimulating factor (GM-CSF) increases protection against malaria, and we have characterized in detail the increased immune responses due to GM-CSF. PyCSP1012 plasmid alone protected 28% of mice, and protection increased to 58% when GM-CSF was added (p < 0.0001). GM-CSF plasmid alone did not protect, and control plasmid expressing inactive GM-CSF did not enhance protection. GM-CSF plasmid increased Abs to PyCSP of IgG1, IgG2a, and IgG2b isotypes, but not IgG3 or IgM. IFN-gamma responses of CD8+ T cells to the PyCSP 280-288 amino acid epitope increased but CTL activity did not change. The most dramatic changes after adding GM-CSF plasmid were increases in Ag-specific IL-2 production and CD4+ T cell proliferation. We hypothesize that GM-CSF may act on dendritic cells to enhance presentation of the PyCSP Ag, with enhanced IL-2 production and CD4+ T cell activation driving the increases in Abs and CD8+ T cell function. Recombinant GM-CSF is already used in humans for medical purposes, and GM-CSF protein or plasmids may be useful as enhancers of DNA vaccines.
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PMID:A plasmid encoding murine granulocyte-macrophage colony-stimulating factor increases protection conferred by a malaria DNA vaccine. 972 27

A flow cytometric phagocytosis assay was established to investigate the role of anti-merozoite antibody, complement, and cytokines on the phagocytosis of Plasmodium falciparum merozoites by human neutrophils. This assay involved allowing fluorescein isothiocyanate-labeled merozoites to interact with phagocytes and analysis of the cells on a FACScan with Lysis II software. To differentiate the proportion of neutrophil surface-bound merozoites from the merozoites ingested by neutrophils, the fluorescence of bound merozoites was quenched by adding trypan blue. The data showed that sera from malaria-immune individuals in the Solomon Islands and Papua New Guinea promoted merozoite engulfment by neutrophils. The cytokines tumor necrosis factor alpha, gamma interferon, granulocyte-macrophage colony-stimulating factor, and interleukin-1beta significantly increased the amount and the rate of merozoite phagocytosis by neutrophils. Optimum merozoite phagocytosis occurred when both cytokines and anti-malarial antibody were present.
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PMID:Opsonization and phagocytosis of Plasmodium falciparum merozoites measured by flow cytometry. 1061 69

The contribution of granulocyte-macrophage colony-stimulating factor (GM-CSF), a hematopoietic and immunoregulatory cytokine, to resistance to blood-stage malaria was investigated by infecting GM-CSF-deficient (knockout [KO]) mice with Plasmodium chabaudi AS. KO mice were more susceptible to infection than wild-type (WT) mice, as evidenced by higher peak parasitemia, recurrent recrudescent parasitemia, and high mortality. P. chabaudi AS-infected KO mice had impaired splenomegaly and lower leukocytosis but equivalent levels of anemia compared to infected WT mice. Both bone marrow and splenic erythropoiesis were normal in infected KO mice. However, granulocyte-macrophage colony formation was significantly decreased in these tissues of uninfected and infected KO mice, and the numbers of macrophages in the spleen and peritoneal cavity were significantly lower than in infected WT mice. Serum levels of gamma interferon (IFN-gamma) were found to be significantly higher in uninfected KO mice, and the level of this cytokine was not increased during infection. In contrast, IFN-gamma levels were significantly above normal levels in infected WT mice. During infection, tumor necrosis factor alpha (TNF-alpha) levels were significantly increased in KO mice and were significantly higher than TNF-alpha levels in infected WT mice. Our results indicate that GM-CSF contributes to resistance to P. chabaudi AS infection and that it is involved in the development of splenomegaly, leukocytosis, and granulocyte-macrophage hematopoiesis. GM-CSF may also regulate IFN-gamma and TNF-alpha production and activity in response to infection. The abnormal responses seen in infected KO mice may be due to the lack of GM-CSF during development, to the lack of GM-CSF in the infected mature mice, or to both.
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PMID:Granulocyte-macrophage colony-stimulating factor-deficient mice have impaired resistance to blood-stage malaria. 1111 98

During pregnancy, a local and systemic Th2 bias of maternal immunity favors Th1-dependent infections such as malaria. This study measured cytokines secreted in cultures of chorionic villi, placental blood cells (PBC), and serum in term placentas from 88 malaria-infected and -noninfected Cameroon women. Interleukin (IL)--2 and --4 were consistently low; IL-1 beta, IL-6, granulocyte-macrophage colony-stimulating factor, and transforming growth factor (TGF)--beta 2 were highest in villi cultures. Tumor necrosis factor (TNF)--alpha, interferon (IFN)--gamma, and IL-10 were highest in PBC cultures. Malaria placental infection increased Th1-type cytokines, whereas Th2-type cytokines and TGF-beta 2 were unchanged. Addition of lipopolysaccharide or infected erythrocytes to cultures increased TNF-alpha, IL-1 beta, IL-6, and IL-10 secretions but not those of IFN-gamma and IL-4. Overall, Plasmodium falciparum induced a placental immune response involving both Th1- and Th2-type cell activation. Although the Th1 pathway was favored, IL-10 secretion was also increased, and this increase should be effective in protecting the placenta by controlling the negative effects of Th1 cytokines on pregnancy.
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PMID:Plasmodium falciparum induces a Th1/Th2 disequilibrium, favoring the Th1-type pathway, in the human placenta. 1131 91

The protective effect of co-administration of recombinant mouse granulocyte-macrophage colony-stimulating factor (rmGM-CSF) and synthetic peptide met-enkephalin (M-ENK) against blood-induced Plasmodium berghei infection in Swiss mice was investigated. Mice co-administered with rmGM-CSF (10.0 mug/kg) and M-ENK (2.0 mg/kg) x 3/day, i.p., beginning on day -1 and continuing through day +4 after the initiation of infection, showed significant suppression (p < 0.05) (sometimes even complete elimination) of parasitaemia compared to vehicle-treated controls. However, when administered separately, neither of these agents induced any detectable protective effect. Surprisingly, mice similarly co-administered with rmGM-CSF (10.0 mug/kg) and higher doses of M-ENK (10.0 mg/kg), showed no protection. Polyclonal neutralizing (100%) antibody to rmGM-CSF abrogated the combined protective effect of these agents. Additionally, naloxone (10.0 mg/kg/day x 6, i.p.), a non-selective, opioid receptor antagonist, also blocked the combined protection. Mice that survived the challenge showed a significant increase (p < 0.05) in total circulating leukocytes counts, and the pool-size and the phagocytic activity of both the peritoneal and splenic macrophages, ex vivo. Silica (3.0 mg/mouse, i.v.) abrogated the combined protective effect of rmGM-CSF and M-ENK. These results indicate that co-administration of rmGM-CSF and dose dependent quantities of M-ENK in P. berghei-infected mice can protect against malaria, apparently through macrophage-mediated mechanisms.
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PMID:Protection of mice from malaria after co-administration of recombinant mouse granulocyte-macrophage colony- stimulating factor and methionine-enkephalin. 1156 34

The persistence of immunity to malaria induced in mice by a heterologous DNA priming and poxvirus boosting regimen was characterized. Mice were immunized by priming with DNA vaccine plasmids encoding the Plasmodium yoelii circumsporozoite protein (PyCSP) and murine granulocyte-macrophage colony-stimulating factor and boosting with recombinant vaccinia encoding PyCSP. BALB/c mice immunized with either high-dose (100 microg of p PyCSP plus 30 microg of pGM-CSF) or low-dose (1 microg of p PyCSP plus 1 microg of pGM-CSF DNA) priming were protected against challenge with 50 P. yoelii sporozoites. Protection 2 weeks after immunization was 70 to 100%, persisted at this level for at least 20 weeks, and declined to 30 to 40% by 28 weeks. Eight of eight mice protected at 20 weeks were still protected when rechallenged at 40 weeks. The antigen (Ag)-specific effector CD8(+)-T-cell population present 2 weeks after boosting had ex vivo Ag-specific cytolytic activity, expressed both gamma interferon (IFN-gamma) and tumor necrosis factor alpha, and constituted 12 to 20% of splenic CD8(+) T cells. In contrast, the memory CD8(+)-Ag-specific-cell population at 28 weeks lacked cytolytic activity and constituted only 6% of splenic CD8(+) T cells, but at the single-cell level it produced significantly higher levels of IFN-gamma than the effectors. High levels of Ag- or parasite-specific antibodies present 2 weeks after boosting had declined three- to sevenfold by 28 weeks. Low-dose priming was similarly immunogenic and as protective as high-dose priming against a 50-, but not a 250-, sporozoite challenge. These results demonstrate that a heterologous priming and boosting vaccination can provide lasting protection against malaria in this model system.
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PMID:Persistence of protective immunity to malaria induced by DNA priming and poxvirus boosting: characterization of effector and memory CD8(+)-T-cell populations. 1206 88

We tested a cytokine-enhanced, multiantigen, DNA priming and poxvirus boosting vaccine regimen for prevention of malaria in the Plasmodium knowlesi-rhesus macaque model system. Animals were primed with a mixture of DNA plasmids encoding two preerythrocytic-stage proteins and two erythrocytic-stage proteins from P. knowlesi and combinations of the cytokines granulocyte-macrophage colony-stimulating factor, interleukin-4, and tumor necrosis factor alpha and were boosted with a mixture of four recombinant, attenuated vaccinia virus strains encoding the four P. knowlesi antigens. Two weeks after boosting, the geometric mean immunofluorescence titers in the immunized groups against sporozoites and infected erythrocytes ranged from 160 to 8,096 and from 1,810 to 5,120, respectively. The geometric mean anti-P. knowlesi circumsporozoite protein (PkCSP) titers ranged from 1,761 to 24,242. Peripheral blood mononuclear cells (PBMC) from the immunized monkeys produced gamma interferon (IFN-gamma) in response to incubation with pooled peptides from the PkCSP at frequencies of 10 to 571 spot-forming cells/10(6) PBMC. Following challenge with 100 infectious P. knowlesi sporozoites, 2 of 11 immunized monkeys were sterilely protected, and 7 of the 9 infected monkeys resolved their parasitemias spontaneously. In contrast, all four controls became infected and required treatment for overwhelming parasitemia. Early protection was strongly associated with IFN-gamma responses against a pool of peptides from the preerythrocytic-stage antigen, PkCSP. These findings demonstrate that a multistage, multiantigen, DNA priming and poxvirus boosting vaccine regimen can protect nonhuman primates from an otherwise lethal malaria sporozoite challenge.
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PMID:Protection of rhesus macaques against lethal Plasmodium knowlesi malaria by a heterologous DNA priming and poxvirus boosting immunization regimen. 1211 42

We have earlier shown that recombinant mouse granulocyte-macrophage colony-stimulating factor (rmGM-CSF) and methionine-enkephalin co-treatment can protect mice from malaria. We now report the bioimmunotherapeutic effect of rmGM-CSF and a synthetic enkephalin fragment peptide Tyr-Gly-Gly (TGG) co-treatment on blood-induced Plasmodium berghei infection in Swiss mice. Mice were completely aparasitimic following co-treatment with rmGM-CSF (10.0 microg/kg) and TGG (2.0 mg/kg x 3 per day, intraperitoneally (i.p.)) starting from day -1 to day +4; however, in monotherapy, neither of these agents showed any detectable bioimmunotherapeutic effect. Curiously, similar co-treatment with rmGM-CSF (10.0 microg/kg) and higher doses of TGG (10.0 mg/kg) did not protect the mice. The combined bioimmunotherapeutic effect of these agents was abrogated by the separate administration each of rabbit neutralizing anti-rmGM-CSF antibody, non-selective opioid receptor antagonist naltrexone (10.0 mg/kg x 6 per day, i.p.), and silica (3.0 mg per mouse, intravenously (i.v.)). The peritoneal and splenic macrophages from the protected mice showed a significant (P<0.05) increase in their pool-size and the phagocytic activity, ex vivo. Furthermore, the protected mice, as compared to the unprotected ones, showed a significant (P<0.05) maximum increase in their serum nitrate and nitrite, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) levels in their splenic homogenates, on the day before the beginning of the resolution of parasitaemia. Selective inhibitors of both inducible (aminoguanidine) and all forms (L-N(G)-monomethyl arginine) of nitric oxide (NO) synthase, significantly (P<0.05) augmented the mortality of co-treated mice, suggesting the role of NO in protection. These data show that, in P. berghei-infected mice, co-treatment with rmGM-CSF and conditional doses of TGG can impart protection, apparently through partly NO-dependent and macrophage-mediated mechanism(s).
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PMID:Bioimmunotherapy of rodent malaria: co-treatment with recombinant mouse granulocyte-macrophage colony-stimulating factor and an enkephalin fragment peptide Tyr-Gly-Gly. 1515 86


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