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Tumor necrosis factor-induced hepatic DNA fragmentation as an early marker of T cell-dependent liver injury in mice

Tumor necrosis factor-induced hepatic DNA fragmentation as an early marker of T cell-dependent liver injury in mice

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GANTNER, Florian, Marcel LEIST, Sabine JILG, Paul G. GERMANN, Marina A. FREUDENBERG, Gisa TIEGS, 1995. Tumor necrosis factor-induced hepatic DNA fragmentation as an early marker of T cell-dependent liver injury in mice. In: Gastroenterology. Elsevier. 109(1), pp. 166-176. ISSN 0016-5085. eISSN 1528-0012. Available under: doi: 10.1016/0016-5085(95)90282-1

@article{Gantner1995-07Tumor-51277, title={Tumor necrosis factor-induced hepatic DNA fragmentation as an early marker of T cell-dependent liver injury in mice}, year={1995}, doi={10.1016/0016-5085(95)90282-1}, number={1}, volume={109}, issn={0016-5085}, journal={Gastroenterology}, pages={166--176}, author={Gantner, Florian and Leist, Marcel and Jilg, Sabine and Germann, Paul G. and Freudenberg, Marina A. and Tiegs, Gisa} }

Leist, Marcel Freudenberg, Marina A. Jilg, Sabine terms-of-use Tiegs, Gisa 2020-10-09T07:54:14Z 1995-07 Germann, Paul G. 2020-10-09T07:54:14Z Freudenberg, Marina A. Gantner, Florian Tiegs, Gisa Gantner, Florian Germann, Paul G. Tumor necrosis factor-induced hepatic DNA fragmentation as an early marker of T cell-dependent liver injury in mice Leist, Marcel Jilg, Sabine Background & Aims:<br />The injection of mice with anti-CD3 monoclonal antibody causes activation of T lymphocytes and leads to a lethal shock syndrome. The aim of this study was to investigate T cell-dependent, cytokine-mediated target cell death that leads to organ injury.<br /><br />Methods:<br />The injection of mice with anti-CD3 monoclonal antibody causes activation of T lymphocytes and leads to a lethal shock syndrome. The aim of this study was to investigate T cell-dependent, cytokine-mediated target cell death that leads to organ injury. Anti-CD3 monoclonal antibody or staphylococcal enterotoxin B was injected into mice sensitized by d-galactosamine. Liver injury was assessed biochemically and histologically, and circulating cytokines were determined.<br /><br />Results:<br />Mice sensitized with d-galactosamine developed severe liver injury within 8 hours after injection of anti-CD3 monoclonal antibody or staphylococcal enterotoxin B. Apoptotic bodies and chromatin condensation were detectable 5 hours after anti-CD3 monoclonal antibody challenge. DNA fragmentation in the liver preceded the increase in plasma alanine aminotransferase activity. Anti-CD3 monoclonal antibody induced the release of tumor necrosis factor and other cytokines. Passive immunization against tumor necrosis factor or pretreatment with immunosuppressive drugs protected mice from liver injury. Liver injury associated with apoptotic cell death and DNA fragmentation was also noted in d-galactosamine-sensitized mice injected with staphylococcal enterotoxin B.<br /><br />Conclusions:<br />Tumor necrosis factor-induced hepatic apoptosis followed by necrosis may represent a general pathomechanism of T-cell shock models using d-galactosamine-sensitized mice. eng

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