gms | German Medical Science

131. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

25.03. - 28.03.2014, Berlin

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Augmenter of Liver Regeneration attenuates CD4+ T cell recruitment and hepatocellular injury after ischemia-reperfusion of the liver

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  • Andrej Khandoga - Klinikum der Universität München, Chirurgische Klinik Großhadern, München
  • Emil Iskandarov - Klinikum der Universität München, Chirurgische Klinik Großhadern, München
  • Konstantin Mende - Klinikum der Universität München, Chirurgische Klinik Großhadern, München
  • Dirk Rosentreter - Klinikum der Universität München, Chirurgische Klinik Großhadern, München
  • Celine Shelcher - Klinikum der Universität München, Chirurgische Klinik Großhadern, München
  • Karl-Walter Jauch - Klinikum der Universität München, Chirurgische Klinik Großhadern, München
  • Markus Rentsch - Klinikum der Universität München, Chirurgische Klinik Großhadern, München
  • Wolfgang Thasler - Klinikum der Universität München, Chirurgische Klinik Großhadern, München

Deutsche Gesellschaft für Chirurgie. 131. Kongress der Deutschen Gesellschaft für Chirurgie. Berlin, 25.-28.03.2014. Düsseldorf: German Medical Science GMS Publishing House; 2014. Doc14dgch542

doi: 10.3205/14dgch542, urn:nbn:de:0183-14dgch5427

Veröffentlicht: 21. März 2014

© 2014 Khandoga et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.

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Text

Introduction: Augmenter of Liver Regeneration (ALR), a protein synthesized in the liver is suggested to be protective against oxidative stress-induced cell death. Hepatic ischemia-reperfusion (I/R) injury is triggered by reactive oxygen species. CD4+ T cells play a critical role during hepatic I/R. The aim of this study was to analyse the impact of ALR on CD4 T cell migration and I/R injury in vivo.

Material and methods: C57BL6 mice were subjected to warm hepatic ischemia for 90 min. Either recombinant ALR (100 µg/kg) or vehicle were administered to mice prior ischemia. Sham-operated animals served as controls (n=7 each group). Freshly isolated and fluorescence-labelled CD4+ T cells were infused intraarterially, their migration was quantified in hepatic microvessels using intravital microscopy. ALT/AST (plasma) and caspase-3 (tissue) activities were determined as markers of hepatocellular necrotic and apoptotic injury after 60 and 240 min of reperfusion.

Results: Hepatic I/R led to a significant enhancement of CD4+ T cell recruitment in hepatic sinusoids (9.2±0.7/acinus) as compared to the sham-operated mice (2.8±0.2/acinus). The plasma activity of AST and ALT (3938±610 and 1615±457 U/L, respectively) as well as caspase-3 activity in tissue (125.8±4.5 RFU/min/µg protein) were dramatically increased. In ALR-treated group, however, CD4 T cell trafficking in the hepatic microvasculature was attenuated (p<0.05). This effect was associated with a significant reduction of tissue injury (liver enzymes and caspase-3 activity).

Conclusion: Our in vivo data show that ALR has a therapeutic potential against postischemic liver injury. As a mechanism we suggest a direct protective effect of ALR on apoptotic and necrotic death of hepatocytes as well as attenuation of inflammatory cell influx into the postischemic tissue.