TY - JOUR
T1 - Hepatic ischemia/reperfusion injury - A fresh look
AU - Fondevila, Constantino
AU - Busuttil, Ronald W.
AU - Kupiec-Weglinski, Jerzy W.
N1 - Funding Information:
This work was supported by NIH Grants RO1 AI42223 and RO1 AI23847 and by The Dumont Research Foundation. C.F. is the recipient of the Fulbright Foundation Award.
PY - 2003/4
Y1 - 2003/4
N2 - Ischemia/reperfusion (I/R) injury is a multifactorial process that affects graft function after liver transplantation. An understanding of the mechanisms involved in I/R injury is essential for the design of therapeutic strategies to improve the outcome of liver transplantation. The generation of reactive oxygen species subsequent to reoxygenation inflicts tissue damage and initiates a cascade of deleterious cellular responses leading to inflammation, cell death, and ultimate organ failure. Increased experimental evidence has suggested that Kupffer cells and T cells mediate the activation of neutrophil inflammatory responses. Activated neutrophils infiltrate the injured liver in parallel with increased expression of adhesion molecules on endothelial cells. The heme oxygenase system is among the most critical of the cytoprotective mechanisms activated during cellular stress, exerting antioxidant and anti-inflammatory functions, modulating the cell cycle, and maintaining the microcirculation. Finally, the activation of toll-like receptors on Kupffer cells may play a fundamental role in exploring new therapeutic strategies based on the concept that hepatic I/R injury represents a case for a host "innate" immunity.
AB - Ischemia/reperfusion (I/R) injury is a multifactorial process that affects graft function after liver transplantation. An understanding of the mechanisms involved in I/R injury is essential for the design of therapeutic strategies to improve the outcome of liver transplantation. The generation of reactive oxygen species subsequent to reoxygenation inflicts tissue damage and initiates a cascade of deleterious cellular responses leading to inflammation, cell death, and ultimate organ failure. Increased experimental evidence has suggested that Kupffer cells and T cells mediate the activation of neutrophil inflammatory responses. Activated neutrophils infiltrate the injured liver in parallel with increased expression of adhesion molecules on endothelial cells. The heme oxygenase system is among the most critical of the cytoprotective mechanisms activated during cellular stress, exerting antioxidant and anti-inflammatory functions, modulating the cell cycle, and maintaining the microcirculation. Finally, the activation of toll-like receptors on Kupffer cells may play a fundamental role in exploring new therapeutic strategies based on the concept that hepatic I/R injury represents a case for a host "innate" immunity.
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U2 - 10.1016/S0014-4800(03)00008-X
DO - 10.1016/S0014-4800(03)00008-X
M3 - Review article
C2 - 12710939
AN - SCOPUS:0037387986
VL - 74
SP - 86
EP - 93
JO - Experimental and Molecular Pathology
JF - Experimental and Molecular Pathology
SN - 0014-4800
IS - 2
ER -