Glycin minimiert Leukozyten-Endothel-Interaktion nach warmer Ischämie durch Inaktivierung der Kupfferzellen

Hepatic microcirculation is disturbed after warm ischemia via mechanisms including Kupffer cell-dependent injury which cannot be prevented during major abdominal surgery, i.e. liver resection or transplantation. Since glycine, a non-toxic amino acid, prevents Kupffer cell-activation this study was designed to assess its impact on leukocyte-endothelium interaction in detail. Sprague-Dawley rats (200 – 230 g) were infused with glycine (1.5 ml; 300 mM) to increase serum glycine levels about 4-fold to 1.2 ± 0.1 mM (p < 0.05) compared with controls treated with isonitrogenous valine, an amino acid without effects on Kupffer cells. Subsequently, warm ischemia of the left liver lobule was induced for 60 minutes. In vivo microscopy immediately after warm ischemia / reperfusion revealed that glycine totally prevented permanent adhesion of leukocytes in postsinusoidal venules (p < 0.05) and significantly reduced this phenomenon in sinusoids from 267 ± 43/mm2 in controls to 66 ± 13/mm2. Further, at 2 hours after warm ischemia glycine significantly reduced AST, ALT and LDH from 375 ± 24 U/l, 402 ± 27 U/l and 3373 ± 351 U/l in controls to 211 ± 27 U/1, 223 ± 31 U/1 and 1374 ± 238 U/1 respectively. Warm ischemia increased both phagocytosis of fluorescent latex beads (1 μm) more than 3.5-fold to 85 ± 6/microscopic field (p < 0.05) and [Ca2+]i in Kupffer cells about 2-fold to 190 ± 8 nM (p < 0.05) which indicates Kupffer cell-activation, being totally prevented with glycine. These results demonstrate for the first time that glycine dramatically reduces injury to livers after warm ischemia via mechanisms including minimized Kupffer cell-mediated leukocyte-endothelium-interaction.