Liver transplantation and hepatic sinusoidal cells

Primary graft non-function of the liver is one of the common causes of retransplantation. Although the mechanism of primary graft non-function is not fully understood, a potent elucidative pathogenesis is microcirculatory disturbance due to sinusoidal damage during cold preservation and reperfusion. In this article, we discuss the possible participation of sinusoidal endothelial cells and Kupffer cells (KC) in the cold preservation/reperfusion injury. Kupffer cell activation and endothelial damage were developed during the cold preservation with subsequent reperfusion. Activated KC produced a large quantity of tumour necrosis factor (TNF)alpha, and then increased ICAM-1 expression in sinusoidal endothelial cells. The reperfusion experiment showed that hypercoagulability and leucocyte adherence in the liver are strongly involved in reperfusion injury, and that KC blockade as well as anti-TNF alpha antibody and anti-ICAM-1 antibody ameliorate the injury in association with a reduction of both fibrin deposition and leucocyte accumulation. Ultrastructural observation also revealed the beneficial effect of KC blockade on the maintenance of sinusoidal endothelial cells. Furthermore, the thromboxane A2-thromboxane A2 receptor system in the sinusoid was also found to participate in this pathogenesis. Thus, these results suggested that cold preservation/reperfusion injury is due to sinusoidal microcirculatory disturbance, which is, at least in part, induced by communication between activated KC and sinusoidal endothelial cells through, among others, ICAM-1, cytokines and prostanoids.