Zusammenfassung
Inhibition or destruction of Kupffer cells (KC) may protect against ischemia-reperfusion (IR) induced primary graft nonfunction (PNF) in liver transplantation. Besides KC activation, PNF is characterized by microvascular perfusion failure, intrahepatic leukocyte accumulation, cell death and hepatocellular dysfunction. KCs can be inactivated by different agents including gadolinium chloride ...
Zusammenfassung
Inhibition or destruction of Kupffer cells (KC) may protect against ischemia-reperfusion (IR) induced primary graft nonfunction (PNF) in liver transplantation. Besides KC activation, PNF is characterized by microvascular perfusion failure, intrahepatic leukocyte accumulation, cell death and hepatocellular dysfunction. KCs can be inactivated by different agents including gadolinium chloride (GdCI3), methyl palmitate (MP) and glycine. The effects of three KC inactivators on IR-injury after rat liver transplantation were compared in the present study. Lewis liver donors were treated with GdCI3, MP, glycine or saline (control). Liver grafts were transplanted following 24 h storage (UW solution). KC populations and IR damage were assessed by histologic analysis, quantitative real-time polymerase chain reaction (RT-PCR) and intravital microscopy. The number of hepatic ED-1 positive macrophages was diminished after GdCI3 (114.8 +/- 4.4/mm(2) liver tissue) and NIP treatment (176.0 +/- 5.0), versus the glycine (263.9 +/- 5.5) and control (272.1 +/- 5.6) groups. All three treatment modalities downregulated phagocytic activity for latex particles, paralleled by reduced microvascular injury (acinar perfusion index, GdCI3: 0.75 +/- 0.03; MP: 0.83 +/- .03; glycine: 0.84 +/- 0.03; 0.63 +/- 0.03). Quantitative RT-PCR revealed elevated myeloperoxidase mRNA after glycine versus GdCI3 and MP pretreatment (3.2- and 3.4-fold, P = 0.011, respectively), without difference to controls (2.9-fold of glycine). TNF alpha-mRNA was reduced after glycine- (5.2-fold), GdCI3-(19.7-fold), MP-treatment (39.5-fold) compared with controls. However, profound prevention of intrahepatic cell death and liver graft failure was solely achieved with glycine preconditioning. Different than GdCI3 and MP, glycine modulates rather than destroys KCs. Glycine appears to preserve cell viability and to TNF alpha/leukocyte dependent organ regeneration capacity, which is related to increase graft survival following liver transplantation.
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