The Experts below are selected from a list of 25482 Experts worldwide ranked by ideXlab platform
Gisa Tiegs - One of the best experts on this subject based on the ideXlab platform.
-
interferon gamma plays a critical role in t cell dependent liver injury in mice initiated by Concanavalin a
Gastroenterology, 1996Co-Authors: S Kusters, Florian Gantner, Gerald Kunstle, Gisa TiegsAbstract:Abstract BACKGROUND & AIMS: T cell-dependent liver injury involving endogenous tumor necrosis factor (TNF) alpha can be induced by either Concanavalin A in naive mice or by activating anti-CD3 antibody or staphylococcal enterotoxin B in D-galactosamine-sensitized mice. In this study, the role of interferon gamma (IFN-gamma) in these T-cell models was addressed. METHODS: Mice were pretreated with a neutralizing anti-mouse IFN-gamma antiserum before injection of T cell-activating agents. Plasma cytokine and transaminase levels were determined. Apoptotic cell death was assessed by hepatic DNA fragmentation. RESULTS: Anti-IFN- gamma antiserum significantly protected mice from Concanavalin A- induced liver injury. Circulating IFN-gamma was completely suppressed, and TNF was reduced by 50%. Recombinant TNF-alpha administered to mice treated with Concanavalin A and anti-IFN-gamma antiserum failed to initiate liver injury. Similar results were obtained with recombinant IFN-gamma in Concanavalin A-challenged mice under the condition of TNF neutralization. Neither hepatic DNA fragmentation nor release of transaminases was inhibited by anti-IFN-gamma antiserum when liver injury was induced by staphylococcal enterotoxin B or anti-CD3 antibody in D-galactosamine-sensitized mice. CONCLUSIONS: Both TNF as well as IFN-gamma are critical mediators of liver injury in Concanavalin A- treated mice, whereas hepatic DNA fragmentation and liver failure in the D-galactosamine models depend only on TNF. (Gastroenterology 1996 Aug;111(2):462-71)
-
Concanavalin a induced t cell mediated hepatic injury in mice the role of tumor necrosis factor
Hepatology, 1995Co-Authors: Florian Gantner, Marcel Leist, Ansgar Wilhelm I Lohse, Paul Georg Germann, Gisa TiegsAbstract:Abstract Concanavalin A activates T lymphocytes in vitro and causes T-cell-dependent hepatic injury in mice. T lymphocytes were previously identified as effector cells of Concanavalin A—induced liver injury. Here we report that hepatic injury is characterized by apoptotic cell death. On Concanavalin A challenge, the cytokines tumor necrosis factor-α (TNFα), interleukin-2, granulocyte macrophage-colony stimulating factor, and interferon-γ were detectable in the circulation of the mice. Pretreatment of mice with anti-mouse TNF-α antiserum protected them from Concanavalin A-induced liver injury. Nude mice failed to release TNF-α or interleukin-2 after Concanavalin A challenge and were protected from liver injury. Lymph node cell transfer from responder mice to resistant nude mice resulted in susceptibility of the latter towards Concanavalin A, i.e., to induction of cytokine release and hepatotoxicity. These experiments suggest that immunocompetent T cells play a pivotal role in Concanavalin A—stimulated TNF-α release in vivo . After intravenous administration of fluorescein isothiocyanate-labeled Concanavalin A to mice, the most fluorescence was found within the liver. In vitro , Concanavalin A stimulation of separate cultures of mouse lymph node cells or nonparenchymal liver cells induced the release of minute amounts of TNF, whereas stimulation of cocultures of these cells resulted in production of substantial amounts of TNF-α. These findings may explain the hepatotropic effect of Concanavalin A. In conclusion, T-cell-dependent Concanavalin A-induced apoptotic liver injury in mice is related to immunological and cytokinemediated disorders and possibly to autoreactive hepatic processes.
Bernhard Schlesier - One of the best experts on this subject based on the ideXlab platform.
-
crystal structure of Concanavalin b at 1 65 a resolution an inactivated chitinase from seeds of canavalia ensiformis
Journal of Molecular Biology, 1995Co-Authors: Michael Hennig, Johan N Jansonius, Anke Terwisscha C Van Scheltinga, Bauke W Dijkstra, Bernhard SchlesierAbstract:Seeds of Canavalia ensiformis (jack bean) contain besides large amounts of canavalin and Concanavalin A, a protein with a molecular mass of 33,800 which has been named Concanavalin B. Although Concanavalin B shares about 40% sequence identity with plant chitinases belonging to glycosyl hydrolase family 18, no chitinase activity could be detected for this protein. To resolve this incongruity Concanavalin B was crystallised and its three-dimensional structure determined at 1.65 Angstrom (1 Angstrom = 0.1 nm) resolution. The structure consists of a single domain with a (beta/alpha)(8) topology A 30 amino acid residue long loop occurs between the second beta-strand of the barrel and the second alpha-helix. This extended loop is unusual for the (beta/alpha)(8) topology but appears in a similar conformation in the structures of the seed protein narbonin and several chitinases as well. Two non-proline cis-peptide bonds are present in the structure of Concanavalin B: Ser34-Phe, and Trp265-Asn. This structural feature is rarely observed in proteins, but could also be identified in the three-dimensional structures of family 18 chitinases and narbonin in coincident positions. In the chitinases the aromatic residues of the non-proline cis-peptides have been proposed to have a function in the binding of the substrate. The region in Concanavalin B, where in chitinases the active site is located, shows two significant differences. First, the catalytic glutamic acid is a glutamine in Concanavalin B. Second, although part of the substrate binding cleft of the chitinases is present in Concanavalin B, it is much shorter. From this we conclude that Concanavalin B and family 18 chitinases are closely related, but that Concanavalin B has lost its enzymatic function. It still may act as a carbohydrate binding protein, however. (C) 1995 Academic Press Limited
-
crystal structure of Concanavalin b at 1 65 a resolution an inactivated chitinase from seeds of canavalia ensiformis
Default journal, 1995Co-Authors: Michael Hennig, Johan N Jansonius, Anke Terwisscha C Van Scheltinga, Bauke W Dijkstra, Bernhard SchlesierAbstract:Seeds of Canavalia ensiformis (jack bean) contain besides large amounts of canavalin and Concanavalin A, a protein with a molecular mass of 33,800 which has been named Concanavalin B. Although Concanavalin B shares about 40% sequence identity with plant chitinases belonging to glycosyl hydrolase family 18, no chitinase activity could be detected for this protein. To resolve this incongruity Concanavalin B was crystallised and its three-dimensional structure determined at 1.65 A (1 A = 0.1 nm) resolution. The structure consists of a single domain with a (β/α)8 topology. A 30 amino acid residue long loop occurs between the second β-strand of the barrel and the second α-helix. This extended loop is unusual for the (β/α)8 topology, but appears in a similar conformation in the structures of the seed protein narbonin and several chitinases as well. Two non-proline cis-peptide bonds are present in the structure of Concanavalin B: Ser34-Phe, and Trp265-Asn. This structural feature is rarely observed in proteins, but could also be identified in the three-dimensional structures of family 18 chitinases and narbonin in coincident positions. In the chitinases the aromatic residues of the non-proline cis-peptides have been proposed to have a function in the binding of the substrate. The region in Concanavalin B, where in chitinases the active site is located, shows two significant differences. First, the catalytic glutamic acid is a glutamine in Concanavalin B. Second, although part of the substrate binding cleft of the chitinases is present in Concanavalin B, it is much shorter. From this we conclude that Concanavalin B and family 18 chitinases are closely related, but that Concanavalin B has lost its enzymatic function. It still may act as a carbohydrate binding protein, however.
Florian Gantner - One of the best experts on this subject based on the ideXlab platform.
-
interferon gamma plays a critical role in t cell dependent liver injury in mice initiated by Concanavalin a
Gastroenterology, 1996Co-Authors: S Kusters, Florian Gantner, Gerald Kunstle, Gisa TiegsAbstract:Abstract BACKGROUND & AIMS: T cell-dependent liver injury involving endogenous tumor necrosis factor (TNF) alpha can be induced by either Concanavalin A in naive mice or by activating anti-CD3 antibody or staphylococcal enterotoxin B in D-galactosamine-sensitized mice. In this study, the role of interferon gamma (IFN-gamma) in these T-cell models was addressed. METHODS: Mice were pretreated with a neutralizing anti-mouse IFN-gamma antiserum before injection of T cell-activating agents. Plasma cytokine and transaminase levels were determined. Apoptotic cell death was assessed by hepatic DNA fragmentation. RESULTS: Anti-IFN- gamma antiserum significantly protected mice from Concanavalin A- induced liver injury. Circulating IFN-gamma was completely suppressed, and TNF was reduced by 50%. Recombinant TNF-alpha administered to mice treated with Concanavalin A and anti-IFN-gamma antiserum failed to initiate liver injury. Similar results were obtained with recombinant IFN-gamma in Concanavalin A-challenged mice under the condition of TNF neutralization. Neither hepatic DNA fragmentation nor release of transaminases was inhibited by anti-IFN-gamma antiserum when liver injury was induced by staphylococcal enterotoxin B or anti-CD3 antibody in D-galactosamine-sensitized mice. CONCLUSIONS: Both TNF as well as IFN-gamma are critical mediators of liver injury in Concanavalin A- treated mice, whereas hepatic DNA fragmentation and liver failure in the D-galactosamine models depend only on TNF. (Gastroenterology 1996 Aug;111(2):462-71)
-
Concanavalin a induced t cell mediated hepatic injury in mice the role of tumor necrosis factor
Hepatology, 1995Co-Authors: Florian Gantner, Marcel Leist, Ansgar Wilhelm I Lohse, Paul Georg Germann, Gisa TiegsAbstract:Abstract Concanavalin A activates T lymphocytes in vitro and causes T-cell-dependent hepatic injury in mice. T lymphocytes were previously identified as effector cells of Concanavalin A—induced liver injury. Here we report that hepatic injury is characterized by apoptotic cell death. On Concanavalin A challenge, the cytokines tumor necrosis factor-α (TNFα), interleukin-2, granulocyte macrophage-colony stimulating factor, and interferon-γ were detectable in the circulation of the mice. Pretreatment of mice with anti-mouse TNF-α antiserum protected them from Concanavalin A-induced liver injury. Nude mice failed to release TNF-α or interleukin-2 after Concanavalin A challenge and were protected from liver injury. Lymph node cell transfer from responder mice to resistant nude mice resulted in susceptibility of the latter towards Concanavalin A, i.e., to induction of cytokine release and hepatotoxicity. These experiments suggest that immunocompetent T cells play a pivotal role in Concanavalin A—stimulated TNF-α release in vivo . After intravenous administration of fluorescein isothiocyanate-labeled Concanavalin A to mice, the most fluorescence was found within the liver. In vitro , Concanavalin A stimulation of separate cultures of mouse lymph node cells or nonparenchymal liver cells induced the release of minute amounts of TNF, whereas stimulation of cocultures of these cells resulted in production of substantial amounts of TNF-α. These findings may explain the hepatotropic effect of Concanavalin A. In conclusion, T-cell-dependent Concanavalin A-induced apoptotic liver injury in mice is related to immunological and cytokinemediated disorders and possibly to autoreactive hepatic processes.
G Murphy - One of the best experts on this subject based on the ideXlab platform.
-
Induction of matrix metalloproteinase activation cascades based on membrane-type 1 matrix metalloproteinase: associated activation of gelatinase A, gelatinase B and collagenase 3.
The Biochemical journal, 1998Co-Authors: Stuart Cowell, J J Reynolds, Marie-pia D'ortho, Carlos López-otín, R M Hembry, Heather Stanton, Vera Knäuper, M.l Stewart, G MurphyAbstract:SW1353 chondrosarcoma cells cultured in the presence of interleukin-1, Concanavalin A or PMA secreted procollagenase 3 (matrix metalloproteinase-13). The enzyme was detected in the culture medium by Western blotting using a specific polyclonal antibody raised against recombinant human procollagenase 3. Oncostatin M enhanced the interleukin-1-induced production of procollagenase 3, whereas interleukin-4 decreased procollagenase 3 synthesis. The enzyme was latent except when the cells had been treated with Concanavalin A, when a processed form of 48 kDa, which corresponds to the active form, was found in the culture medium and collagenolytic activity was detected by degradation of 14C-labelled type I collagen. The Concanavalin A-induced activation of procollagenase 3 coincided with the processing of progelatinase A (matrix metalloproteinase-2) by the cells, as measured by gelatin zymography. In addition, progelatinase B (matrix metalloproteinase-9) was activated when gelatinase A and collagenase 3 were in their active forms. Concanavalin A treatment of SW1353 cells increased the amount of membrane-type-1 matrix metalloproteinase protein in the cell membranes, suggesting that this membrane-bound enzyme participates in an activation cascade involving collagenase 3 and the gelatinases. This cascade was effectively inhibited by tissue inhibitors of metalloproteinases-2 and -3. Tissue inhibitor of metalloproteinases-1, which is a much weaker inhibitor of membrane-type 1 matrix metalloproteinase than tissue inhibitors of metalloproteinases-2 and -3 [Will, Atkinson, Butler, Smith and Murphy (1996) J. Biol. Chem. 271, 17119-17123], was a weaker inhibitor of the activation cascade.
Michael Hennig - One of the best experts on this subject based on the ideXlab platform.
-
crystal structure of Concanavalin b at 1 65 a resolution an inactivated chitinase from seeds of canavalia ensiformis
Journal of Molecular Biology, 1995Co-Authors: Michael Hennig, Johan N Jansonius, Anke Terwisscha C Van Scheltinga, Bauke W Dijkstra, Bernhard SchlesierAbstract:Seeds of Canavalia ensiformis (jack bean) contain besides large amounts of canavalin and Concanavalin A, a protein with a molecular mass of 33,800 which has been named Concanavalin B. Although Concanavalin B shares about 40% sequence identity with plant chitinases belonging to glycosyl hydrolase family 18, no chitinase activity could be detected for this protein. To resolve this incongruity Concanavalin B was crystallised and its three-dimensional structure determined at 1.65 Angstrom (1 Angstrom = 0.1 nm) resolution. The structure consists of a single domain with a (beta/alpha)(8) topology A 30 amino acid residue long loop occurs between the second beta-strand of the barrel and the second alpha-helix. This extended loop is unusual for the (beta/alpha)(8) topology but appears in a similar conformation in the structures of the seed protein narbonin and several chitinases as well. Two non-proline cis-peptide bonds are present in the structure of Concanavalin B: Ser34-Phe, and Trp265-Asn. This structural feature is rarely observed in proteins, but could also be identified in the three-dimensional structures of family 18 chitinases and narbonin in coincident positions. In the chitinases the aromatic residues of the non-proline cis-peptides have been proposed to have a function in the binding of the substrate. The region in Concanavalin B, where in chitinases the active site is located, shows two significant differences. First, the catalytic glutamic acid is a glutamine in Concanavalin B. Second, although part of the substrate binding cleft of the chitinases is present in Concanavalin B, it is much shorter. From this we conclude that Concanavalin B and family 18 chitinases are closely related, but that Concanavalin B has lost its enzymatic function. It still may act as a carbohydrate binding protein, however. (C) 1995 Academic Press Limited
-
crystal structure of Concanavalin b at 1 65 a resolution an inactivated chitinase from seeds of canavalia ensiformis
Default journal, 1995Co-Authors: Michael Hennig, Johan N Jansonius, Anke Terwisscha C Van Scheltinga, Bauke W Dijkstra, Bernhard SchlesierAbstract:Seeds of Canavalia ensiformis (jack bean) contain besides large amounts of canavalin and Concanavalin A, a protein with a molecular mass of 33,800 which has been named Concanavalin B. Although Concanavalin B shares about 40% sequence identity with plant chitinases belonging to glycosyl hydrolase family 18, no chitinase activity could be detected for this protein. To resolve this incongruity Concanavalin B was crystallised and its three-dimensional structure determined at 1.65 A (1 A = 0.1 nm) resolution. The structure consists of a single domain with a (β/α)8 topology. A 30 amino acid residue long loop occurs between the second β-strand of the barrel and the second α-helix. This extended loop is unusual for the (β/α)8 topology, but appears in a similar conformation in the structures of the seed protein narbonin and several chitinases as well. Two non-proline cis-peptide bonds are present in the structure of Concanavalin B: Ser34-Phe, and Trp265-Asn. This structural feature is rarely observed in proteins, but could also be identified in the three-dimensional structures of family 18 chitinases and narbonin in coincident positions. In the chitinases the aromatic residues of the non-proline cis-peptides have been proposed to have a function in the binding of the substrate. The region in Concanavalin B, where in chitinases the active site is located, shows two significant differences. First, the catalytic glutamic acid is a glutamine in Concanavalin B. Second, although part of the substrate binding cleft of the chitinases is present in Concanavalin B, it is much shorter. From this we conclude that Concanavalin B and family 18 chitinases are closely related, but that Concanavalin B has lost its enzymatic function. It still may act as a carbohydrate binding protein, however.