BACKGROUND: The precise mechanisms leading to polymorphonuclear neutrophil (PMN) recruitment and activation in the extended cold-preserved liver after transplantation are not yet fully understood. METHODS: We histologically evaluated the number of accumulated PMNs in graft livers, with varying time periods of cold ischemia (1, 6, and 24 hr in University of Wisconsin solution at 4 degrees C), after liver transplantation in rats. Intragraft expression of macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (CINC) mRNA, as well as immunohistochemical expression of MIP-2 and CINC in the graft liver, were investigated after reperfusion. The levels of MIP-2 and CINC in the hepatic vein, and tumor necrosis factor (TNF)-alpha, which stimulates these chemokine production, were also monitored. RESULTS: The number of accumulated PMNs in sinusoids significantly increased in the 24-hr cold-ischemia group within 3 hr after reperfusion, compared with the 1-hr and 6-hr groups. Serum MIP-2 levels in the 24-hr group significantly increased at 3, 6, and 12 hr after reperfusion, compared with the other groups. Intragraft MIP-2 mRNA was also up-regulated to a greater extent in the 24-hr group. Similarly, serum CINC levels in the 24-hr group significantly increased at 3 hr, compared with the 1-hr group. CINC mRNA also increased as cold-ischemia time was prolonged. Immunohistochemical staining revealed that hepatocytes were the main source of both MIP-2 and CINC protein. In addition, TNF-alpha in the hepatic vein was detected only in the 24-hr group after reperfusion. CONCLUSION: Extended cold preservation of the graft liver might up-regulate MIP-2 and CINC expression of hepatocytes, most probably through elevated TNF-alpha, and might contribute to PMN recruitment and activation after reperfusion.
BACKGROUND: The precise mechanisms leading to polymorphonuclear neutrophil (PMN) recruitment and activation in the extended cold-preserved liver after transplantation are not yet fully understood. METHODS: We histologically evaluated the number of accumulated PMNs in graft livers, with varying time periods of cold ischemia (1, 6, and 24 hr in University of Wisconsin solution at 4 degrees C), after liver transplantation in rats. Intragraft expression of macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (CINC) mRNA, as well as immunohistochemical expression of MIP-2 and CINC in the graft liver, were investigated after reperfusion. The levels of MIP-2 and CINC in the hepatic vein, and tumor necrosis factor (TNF)-alpha, which stimulates these chemokine production, were also monitored. RESULTS: The number of accumulated PMNs in sinusoids significantly increased in the 24-hr cold-ischemia group within 3 hr after reperfusion, compared with the 1-hr and 6-hr groups. Serum MIP-2 levels in the 24-hr group significantly increased at 3, 6, and 12 hr after reperfusion, compared with the other groups. Intragraft MIP-2 mRNA was also up-regulated to a greater extent in the 24-hr group. Similarly, serum CINC levels in the 24-hr group significantly increased at 3 hr, compared with the 1-hr group. CINC mRNA also increased as cold-ischemia time was prolonged. Immunohistochemical staining revealed that hepatocytes were the main source of both MIP-2 and CINC protein. In addition, TNF-alpha in the hepatic vein was detected only in the 24-hr group after reperfusion. CONCLUSION: Extended cold preservation of the graft liver might up-regulate MIP-2 and CINC expression of hepatocytes, most probably through elevated TNF-alpha, and might contribute to PMN recruitment and activation after reperfusion.
Authors: Danielle G Souza; Riccardo Bertini; Angelica T Vieira; Fernando Q Cunha; Steve Poole; Marcello Allegretti; Francesco Colotta; Mauro M Teixeira Journal: Br J Pharmacol Date: 2004-08-09 Impact factor: 8.739
Authors: A E Gelman; M Okazaki; S Sugimoto; W Li; C G Kornfeld; J Lai; S B Richardson; F H Kreisel; H J Huang; J R Tietjens; B H Zinselmeyer; G A Patterson; M J Miller; A S Krupnick; D Kreisel Journal: Am J Transplant Date: 2010-05 Impact factor: 8.086
Authors: Jan Korbecki; Iwona Szatkowska; Patrycja Kupnicka; Wojciech Żwierełło; Katarzyna Barczak; Iwona Poziomkowska-Gęsicka; Jerzy Wójcik; Dariusz Chlubek; Irena Baranowska-Bosiacka Journal: Int J Mol Sci Date: 2022-06-28 Impact factor: 6.208