The Role Of IRAK-4 On Kupffer Cells Activiation Induced By Endotoxin In Transplantative Liver During Ischemia/Reperfusion Phase

Objective: Despite intense research on the development of novel therapeutic strategies, early primary graft dysfunction or poor graft function due to ischemia-reperfusion injury (I/RI) still represents a major problem in clinical liver transplantation, with important implications for patient morbidity and mortality. Substantial evidence indicates that Kupffer cells (KCs), the resident macrophages of the liver, consisted of 80%-90% total mononuclear phagocytes, play a central role in the pathogenesis of liver parenchyma cell damage during reperfusion phase, since activated KCs are capable of releasing numerous mediators, such as tumor necrosis factor (TNF-α) to regulation of hepatic microcirculation, and microcirculatory disturbance is a key factor in enhanced donor liver susceptibility to reperfusion. The most common candidates for liver transplantation are patients with all kinds of end-stage liver diseases combined with high levels of endotoxin or lipopolysacchardes (LPS), an integral component of the cell wall of gram-negative bacilli and being involved in priming and deterioration in I/RI as a potent stimulus for KCs.