Kupffer Cell Function in Ischemic and Nonischemic Livers After Hepatic Partial Ischemia/Reperfusion

Abstract

Hepatic partial ischemic/reperfusion (I/R) injury, in which ischemic and nonischemic areas of the liver are likely to respond to each other after reperfusion, often occurs following hepatobiliary surgical procedures. Kupffer cells (KCs) are considered to play a major role in hepatic I/R injury. To study the activation of KCs in ischemic and nonischemic liver tissues following hepatic I/R, we investigated the superoxide generation and proinflammatory cytokine production of KCs in both liver parts in a rat model of partial hepatic I/R injury. KC superoxide generation in the ischemic and nonischemic lobes was upregulated 6 and 24 h after reperfusion, respectively, and then accelerated. The production of interleukin-1beta (IL-1beta) by KCs in the ischemic lobes increased during the early and late phases, 6 h and 48-72 h after reperfusion, respectively. A late increase in IL-1beta production was also observed in the nonischemic lobes. Production of tumor necrosis factor-alpha (TNF-alpha) increased 6-24h after reperfusion in both lobes. Upregulation of IL-1beta mRNA in the ischemic lobes preceded the upregulation of TNF-alpha mRNA in both lobes. The hepatic partial I/R process results in activation of KCs in ischemic and nonischemic areas of the liver. The KCs are activated during the early phase after reperfusion in the ischemic areas, followed by activation in both the ischemic and nonischemic areas. This could be a cause of liver dysfunction after partial hepatic I/R during surgery.

Prometheus’ Challenge: Molecular, Cellular and Systemic Aspects of Liver Regeneration

“…Soon after, they mediate the activation of platelet adhesion and neutrophil inflammatory response that infiltrates the injured liver and increases the expression of more adhesion molecules on endothelial cells and more generation of reactive oxygen radicals. The methods by which ischemia/reperfusion injury can be diagnosed include ASGP-R ligand on hepatocytes, showing ischemic damage histologically, hepatobiliary scintigraphy, an easy method in clinics, and electron microscopy, the diagnostic gold standard [135][136][137][138][139][140][141][142][143][144][145]. Reactive oxygen radical scavengers can be used to protect ischemia/reperfusion injury syndrome.…”

The Protective Effect of α-Tocopherol and GdCl3 Against Hepatic Ischemia/Reperfusion Injury

“…1,2 Early activation of Kupffer cells enhances the formation of reactive oxygen species and proinflammatory mediators such as tumor necrosis factor-α, interleukin-1, and proteases. 3 The inhibitory effect of gadolinium chloride (GdCl 3 ) against Kupffer cell activation shows potential as a protective intervention in rat models of in vivo hepatic reperfusion injury and isolated perfused livers. [4][5][6][7][8][9][10] It has also been shown that giving GdCl 3 for liver I/R injury decreases the mortality rate, 11 attenuates neutrophil infiltration and decreases myeloperoxidase activity, 12 improves hepatic function, 5,13 reduces platelet accumulation in cold perfused livers, and prevents apoptosis of sinusoidal endothelial cells.…”

Ethanol Preconditioning Reduces Hepatic I/R Injury by Inhibiting the Complement System Activation

“…Hepatic I/R has been shown to generate oxygenderived free radicals by activated Kupffer cells [6,26,27]. A chain reaction of lipid peroxidation initiated by oxygen-derived free radicals compromises cellular viability and ultimately results in tissue injury [28].…”