Hepatic ischemia/reperfusion injury--a fresh look.
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.
Fondevila
Constantino
C
Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Busuttil
Ronald W
RW
Kupiec-Weglinski
Jerzy W
JW
D000818:Animals; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006801:Humans; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D016031:Liver Transplantation / Q000009:adverse effects*; D008954:Models, Biological; D020556:Neutrophil Infiltration; D015427:Reperfusion Injury / Q000209:etiology* / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism
D006419:Heme Oxygenase (Decyclizing)