Abstract
The nuclear repair enzyme poly(ADP-ribose)polymerase (PARP) has been shown to play an important role in the pathogenesis of the inflammatory response. The aim of this in vivo study was to investigate whether PARP participates in the microvascular mechanisms of hepatic ischemia-reperfusion (I/R) injury.
A warm lobar hepatic ischemia was induced for 90 min in C57BL/6xl29Sv wild-type (PARP+ / + , n = 7) and PARP-1-deficient mice (PARP- / - , n = 7). Leukocyte and platelet adherence as well as sinusoidal perfusion were quantitatively analyzed by intravital fluorescence microscopy after 30 min of reperfusion. Sham-operated animals served as controls (n = 7). At the end of the experiments, ASTserum activity was determined. Apoptosis was quantified in vivo by counting of H33342-stained condensed nuclei. Phagocytic activity of Kupffer cells was assessed after application of fluorescence-labeled latex beads.
In PARP + / + mice, I/R caused significantly enhanced leukocyte- and platelet-endothelial cell interactions in post-sinusoidal venules as well as sinusoidal perfusion failure, an increase in AST activities, and apoptosis induction. In contrast, the post-ischemic increase in the number of adherent leukocytes and platelets was significantly attenuated in PARP - / - mice. Concomitantly, the sinusoidal perfusion was improved and the increase in the AST activity as well as in the number of apoptotic cells was lower in PARP - / - mice compared to PARP + / + mice. Furthermore, I/R-induced Kupffer cell activation was slower in PARP −/− mice.
These findings provide evidence that PARP modulates leukocyte- and platelet-endothelial cell interactions in the post-ischemic liver. This anti-adhesive effect is associated with a reduced Kupffer cell activity. Lack of PARP-1 results in an attenuation of hepatic microvascular/cellular I/R damage and apoptosis.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Literatur
Szabo C (1998) Role of poly(ADP-ribose)synthetase in inflammation. Eur J Pharmacol 350: 1–19
Herceg Z, Wang ZQ (2001) Functions of poly(ADP-ribose) polymerase (PARP) in DNA repair, genomic integrity and cell death. Mutat Res 477: 97–110
Author information
Authors and Affiliations
Rights and permissions
Copyright information
© 2002 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Khandoga, A., Enders, G., Biberthaler, P., Krombach, F. (2002). Rolle der Poly(ADP-Ribose)Polymerase bei der Ausbildung des mikrovaskulären Ischämie-Reperfusionsschadens der Leber. In: Chirurgisches Forum 2002. Deutsche Gesellschaft für Chirurgie, vol 31. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-56158-0_87
Download citation
DOI: https://doi.org/10.1007/978-3-642-56158-0_87
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-43300-2
Online ISBN: 978-3-642-56158-0
eBook Packages: Springer Book Archive