Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.1.53 (sialidase)
2,694 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human leucocyte, lymphoblastoid and fibroblast interferons were separately treated with sialidase and the effect of this on their isoelectric focusing was examined using a system in which full dissociation of complexes occurred. Both leucocyte and lymphoblastoid interferons showed a single form with an isoelectric point which was unaltered by treatment with sialidase. In contrast, fibroblast interferon showed three forms which were reduced to one by treatment with the enzyme.
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PMID:Differences in sialic acid content of human interferons. 70 15

When BALB/c mice were treated with a Kampo (Japanese herbal) medicine "Sho-seiryu-to" (SST) (2 g/kg, 10 times) orally from 7 days before to 4 days after the infection and infected with mouse-adapted influenza virus A/PR/8/34 by nasal site-restricted infection, replication of the virus in the nasal cavity and spread of the virus to the lung were efficiently inhibited at 5 days after infection in comparison with water-treated mice. However, another Kampo medicine "Kakkon-to" showed no anti-influenza virus activity in the same condition. The antiviral IgA antibody in the nasal and broncho-alveolar washes of the SST treated mice increased significantly in comparison with that of water-treated control. Oral administration of SST (2 g/kg, 18 times) from 7 days before to 13 days after vaccination also significantly augmented serum hemagglutination-inhibiting antibody by nasal inoculation of influenza HA vaccine (5 micrograms/mouse) that was insufficient to induce antiviral antibody. SST did not inhibit the replication of mouse-adapted influenza virus A/PR/8/34 in Madin-Darby canine kidney cells. SST also did not inhibit the influenza virus sialidase activity against sodium p-nitrophenyl-N-acetyl-alpha-D-neuraminate and hemagglutination by mouse-adapted influenza virus A/PR/8/34. SST showed no influence on interferon production in nasal wash of mice at 5 days after the virus infection. These results suggest that SST confers better protection against influenza virus infection through augmentation of production of antiviral IgA antibody but not direct action to the virus, and can be used as an adjuvant to nasally inoculated influenza HA vaccine.
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PMID:In vivo anti-influenza virus activity of kampo (Japanese herbal) medicine "sho-seiryu-to" and its mode of action. 752 77

The interferon antagonist and growth promotor sarcolectin has affinity for negatively charged carbohydrates. Isolation of cellular binding proteins will be a step to elucidate its physiological significance. Thus, resin-immobilized sarcolectin was employed as affinity ligand for chromatographic fractionation of extract from human placenta. Elution with 0.1 M NH4OH or with 0.1 M N-acetylneuraminic acid and 1 M NaCl resulted primarily in purification of a protein of molecular mass of about 12 kDa according to gel electrophoretic analysis under denaturing conditions in the presence or absence of reductive agent and 12,470 Da by laser desorption mass spectrometry. The native molecular mass, assessed by gel filtration, is approximately 28 kDa. No evidence for detectable post-translational modification by glycosylation was provided by treatment with N-glycosidase F or sialidase and subsequent electrophoretic analysis. The N-terminal sequence of the major sarcolectin-binding protein is identical to that deduced from the cDNA sequence of a human macrophage migration inhibitory factor (MIF), starting from its third amino acid, over the determined stretch of 22 amino acids. Comparison of the calculated molecular mass of 12,221 of this factor to the experimentally determined value of 12,470 excludes any extensive modification of the protein. The sarcolectin-binding protein reduces macrophage migration at a concentration of 100 ng/ml in MIF assays. Recombinant migration inhibitory factor and purified sarcolectin-binding protein reacted equally well with anti-MIF antibody in immunoblot analysis and in assays to block binding to sarcolectin. Binding of biotinylated sarcolectin, too, is nearly identical for the two protein preparations. It is optimal in the range pH 7-9 and is markedly impaired by increasing ionic strength. Chemical modification with group-specific reagents revealed that the integrity of carboxyl groups of the sarcolectin-binding protein and of lysine/arginine groups of sarcolectin are primarily important to maintain binding capacity. In addition to contribute to the understanding of the functional significance of sarcolectin this result provides a convenient procedure to purify a lymphokine.
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PMID:The major binding protein of the interferon antagonist sarcolectin in human placenta is a macrophage migration inhibitory factor. 768 62

Immunization with a plasmid DNA containing the gene encoding the catalytic domain of trans-sialidase (TS) elicits protective immune responses against experimental Trypanosoma cruzi infection. As several studies provided strong evidence that during infection CD4 Th1 and CD8 T cytotoxic type 1 (Tc1) cells are important factors in host resistance, the present study was designed to evaluate which T-cell types were activated in DNA-vaccinated BALB/c mice. We found that bulk cells from DNA-immunized mice had CD4 and CD8 T cells that produced gamma interferon (IFN-gamma) but not interleukin-4 (IL-4) or IL-10. To characterize the TS-specific T cells at the clonal level, we generated CD4 and CD8 clones. We obtained cytotoxic CD4 clones of the Th1 type that secreted large amounts of IFN-gamma but not IL-4 or IL-10. Unexpectedly, we obtained other CD4 clones with a Th2 phenotype, secreting IL-4 and IL-10 but not IFN-gamma. All CD8 clones were cytotoxic and produced IFN-gamma. IL-4 and IL-10 were not secreted by these cells. Using synthetic peptides, we determined a CD8 epitope recognized by several clones as being represented by amino acids IYNVGQVSI. The antiparasitic activity of a CD4 Th1 and a CD8 Tc1 clone was assessed in vitro. CD4 or CD8 T cells significantly inhibited T. cruzi development in infected macrophages or fibroblasts, respectively. We concluded that DNA vaccine efficiently generates potentially protective CD4 Th1 and CD8 Tc1 cells specific for a T. cruzi antigen, therefore reinforcing the possibility of using this strategy for developing a preventive or therapeutic vaccine against Chagas' disease.
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PMID:Predominance of CD4 Th1 and CD8 Tc1 cells revealed by characterization of the cellular immune response generated by immunization with a DNA vaccine containing a Trypanosoma cruzi gene. 1041 49

Infective forms of Trypanosoma cruzi, the parasite that causes Chagas' disease, express on their surface an enzyme denominated trans-sialidase (TS). The present study was designed to evaluate the naturally acquired immune responses to a bacterial recombinant protein representing the catalytic domain of TS in chronically infected chagasic individuals. The cellular immune response was measured by in-vitro T-cell proliferation and by interferon (INF)-gamma, interleukin (IL)-4 and IL-10 production in response to a whole-parasite homogenate and the recombinant protein. The peripheral blood mononuclear cells of 78.6% of 28 chagasic patients responded to the recombinant protein as estimated by T-cell proliferation. With respect to cytokine production, 88% of the cells of the chagasic individuals produced IFN-gamma on stimulation with the recombinant protein. In contrast, IL-4 or IL-10 were minimally produced in response to TS. The cellular immune response was specific because most healthy individuals never exposed to T. cruzi failed to react with this recombinant protein. The plasma of 71.4% or 100% of chagasic patients had IgG antibodies as determined by ELISA or by the presence of TS inhibitory antibodies, respectively. We conclude that the catalytic domain of TS is recognized by IFN-gamma producing type 1 cells and antibodies in a large proportion of patients infected with T. cruzi.
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PMID:Chagasic patients develop a type 1 immune response to Trypanosoma cruzi trans-sialidase. 1060 90

Trypanosoma cruzi currently infects 18 million people, and 30% of those infected develop a chronic inflammatory process that causes significant morbidity or mortality. The major histocompatibility complex class II (MHC-II)-restricted T-cell response is critical to the control of the infection and to the ensuing inflammatory pathology. The specific epitopes or major antigens of this response have not been identified. The parasite simultaneously expresses variant members of the trans-sialidase superfamily. To begin to analyze the MHC-II response to these variant proteins, the response to a single surface protein, SA85-1.1, was initiated. These studies have demonstrated that a biased gamma interferon (IFN-gamma) response to the SA85-1.1 protein develops during T. cruzi infection. In addition, adoptive transfer of a CD4 clone that recognizes an SA85-1.1 epitope, named epitope 1, and immunization with a peptide encoding epitope 1 were protective and suggested that epitope 1 may be immunodominant. In this report IFN-gamma intracellular staining demonstrated that splenocytes from acutely and chronically infected mice, incubated with SA85-1.1 protein or peptides that encode epitope 1, result in IFN-gamma synthesis by 4 to 6% of the splenic CD4 cells. These data indicate that during T. cruzi infection epitope 1 is a major epitope and that 4 to 6% of the CD4 cells are stimulated by a single trans-sialidase superfamily epitope and suggest that a combination of trans-sialidase superfamily proteins combines to stimulate a majority of CD4 cells. These data suggest that during T. cruzi infection the CD4 response to the trans-sialidase superfamily is critical to the protective response and to the ensuing chronic inflammatory pathology.
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PMID:The SA85-1.1 protein of the Trypanosoma cruzi trans-sialidase superfamily is a dominant T-cell antigen. 1081 14

Immunization of BALB/c mice with a plasmid containing the gene for Trypanosoma cruzi trans-sialidase (TS) induced antibodies that inhibited TS enzymatic activity, CD4+ Th1 and CD8+ Tc1 cells, and protective immunity against infection. We used this model to obtain basic information on the requirement of CD4 or CD8 or B-cell epitopes for an effective DNA-induced immunity against T. cruzi infection. For that purpose, mice were immunized with plasmids containing DNA sequences encoding (i) the entire TS protein, (ii) the TS enzymatic domain, (iii) the TS CD4+ T-cell epitopes, (iv) the TS CD8+ T-cell epitope, or (v) TS CD4+ and CD8+ T-cell epitopes. Plasmids expressing the entire TS or its enzymatic domain elicited similar levels of TS-inhibitory antibodies, gamma interferon (IFN-gamma)-producing T cells, and protective immunity against infection. Although the plasmid expressing TS CD4 epitopes was immunogenic, its protective efficacy against experimental infection was limited. The plasmid expressing the CD8 epitope was poorly immunogenic and provided little protective immunity. The reason for the limited priming of CD8+ T cells was due to a requirement for CD4+ T cells. To circumvent this problem, a plasmid expressing both CD4+ and CD8+ T-cell epitopes was produced. This plasmid generated levels of IFN-gamma-producing T cells and protective immunity comparable to that of the plasmid expressing the entire catalytic domain of TS. Our observations suggest that plasmids expressing epitopes recognized by CD4+ and CD8+ T cells may have a better protective potential against infection with T. cruzi.
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PMID:DNA sequences encoding CD4+ and CD8+ T-cell epitopes are important for efficient protective immunity induced by DNA vaccination with a Trypanosoma cruzi gene. 1150 Apr 20

Natural human interferon (hIFN)-gamma has mainly biantennary complex-type sugar chains. Previously, we successfully remodeled its sugar chain structure into: (a) highly branched types; or (b) highly sialylated types, by overexpression of: (a) N-acetylglucosaminyltransferase (GnT)-IV and/or GnT-V; or (b) sialyltransferases, in Chinese hamster ovary (CHO) cells. In addition, we prepared asialo hIFN-gammas by treatment with sialidase in vitro. In the present study, we assessed the bioactivity of remodeled hIFN-gamma in terms of antiviral activity, anticellular activity, and biodistribution. Structural changes to the sugar chains did not have a significant influence on the antiviral and anticellular activities of hIFN-gamma, although the attachment of the sugar chain itself affected both activities. However, the biodistribution differed significantly; the number of exposed galactose residues was the major determinant of the specific distribution to the liver and blood clearance rate of hIFN-gamma. This phenomenon was considered to be mediated by the hepatic asialoglycoprotein receptor (ASGP-R), and we showed a linear, not exponential, enhancement of the distribution to the liver with an increase in the number of exposed galactose residues. We also confirmed this tendency using fibroblast growth factor (FGF). Our observation is not the same as the "glycoside cluster effect." We thus provide important information on the character of modified recombinant glycoproteins.
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PMID:Monitoring biodistribution of glycoproteins with modified sugar chains. 1292 14

Protective immunity against lethal infection is developed when BALB/c or C57BL/6 mice are immunized with plasmids containing genes from the protozoan parasite Trypanosoma cruzi. However, genetic vaccination of the highly susceptible mouse strain A/Sn promoted limited survival after challenge. This observation questioned whether this type of vaccination would be appropriate for highly susceptible individuals. Here, we compared the protective efficacy and the immune response after individual or combined genetic vaccination of A/Sn mice with genes encoding trans-sialidase (TS) or the amastigote surface protein-2 (ASP-2). After challenge, a significant proportion of A/Sn mice immunized with either the asp-2 gene or simultaneously with asp-2 and ts genes, survived infection. In contrast, the vast majority of mice immunized with the ts gene or the vector alone died. Parasitological and histological studies performed in the surviving mice revealed that these mice harbored parasites; however, minimal inflammatory responses were seen in heart and striated muscle. We used this model to search for an in vitro correlation for protection. We found that protective immunity correlated with a higher secretion of interferon- by spleen cells on in vitro restimulation with ASP-2 and the presence of ASP-2-specific CD8 cells. Depletion of either CD4 or CD8 or both T-cell subpopulations prior to the challenge rendered the mice susceptible to infection demonstrating the critical contribution of both cell types in protective immunity. Our results reinforce the prophylactic potential of genetic vaccination with asp-2 and ts genes by describing protective immunity against lethal T. cruzi infection and chronic tissue pathology in a highly susceptible mouse strain.
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PMID:Protective immunity against trypanosoma cruzi infection in a highly susceptible mouse strain after vaccination with genes encoding the amastigote surface protein-2 and trans-sialidase. 1535 42

Immune control of the protozoan parasite Trypanosoma cruzi requires the activation of both CD4+ and CD8+ T cells. We recently identified two T. cruzi trans-sialidase peptides that are targets of approximately 30% of all CD8+ T cells during acute T. cruzi infection in mice. To determine whether CD4+ T cells are required for generation of these dominant CD8+ T-cell responses, major histocompatibility complex class II (MHC II)-deficient mice were infected with the Brazil strain of T. cruzi and examined for the generation of antigen-specific CD8+ T cells. Strong trans-sialidase TSKB18- and TSKB20-specific CD8+ T-cell responses were generated in both the presence and the absence of CD4+ help. However, the magnitudes of the immunodominant TSKB20-specific CD8+ T-cell responses detectable using class I MHC-peptide tetramers were consistently lower in the blood and spleens of MHC II-deficient mice. Spleen cells from infected MHC II-deficient mice produced gamma interferon after in vitro stimulation with T. cruzi peptides at levels similar to those in wild-type mice, and MHC II-deficient mice displayed strong T. cruzi peptide-specific cytotoxic T-lymphocyte activity in vivo. Thus, primary CD8+ T-cell responses in experimental T. cruzi infection are generated in the absence of CD4+ T cells, providing further evidence that T. cruzi directly activates and licenses antigen-presenting cells. Nevertheless, unhelped CD8+ T cells in T. cruzi-infected mice fail to reach the frequencies achieved in the presence of CD4 T-cell help and are unable to prevent acute-phase death of these mice.
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PMID:Limited role for CD4+ T-cell help in the initial priming of Trypanosoma cruzi-specific CD8+ T cells. 1704 5


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