Role of non-parenchymal liver cells in ischaemia-reperfusion liver injury: protective effects of muramyl dipeptide.

It has been suggested that non-parenchymal liver cells play a central role after ischaemia and reperfusion of the liver. Male Lewis rats were subjected to 90 min of warm liver ischaemia. Four groups were constituted: group 1, no treatment; group 2, muramyl dipeptide treatment, activation of Kupffer cells; group 3, dextran sulphate injection, Kupffer cell blockade; and group 4, gadolinium chloride administration, Kupffer cell blockade. Dextran sulphate (4 mg/100 g) and gadolinium chloride (GdCl2, 0.7 mg/100 g) were given intravenously on day 2. MDP was injected intravenously (500 mg/250 g) 24 h before and 10 min after the intervention. Mortality rates were assessed and serum transaminases, histology of the liver and Kupffer cell phagocytic activity were evaluated 6 h after the end of ischaemia. MDP treatment significantly (P < 0.001) reduced mortality (30%) in comparison with the non-treated group (60%). The mortality rate was significantly higher in the dextran sulphate-treated (80%) and gadolinium chloride-treated (90%) groups in comparison with group 1. A significant reduction in transaminase levels was observed after MDP treatment, while blockade of Kupffer cells resulted in higher serum transaminase levels. The extent of necrosis and congestion was improved by MDP administration, while disruption of the vascular and sinusoidal integrity of the liver and extensive areas of necrosis were observed in dextran sulphate and gadolinium chloride-treated rats. Sheep red blood cell 51Cr liver uptake was deeply depressed 6 h after the end of ischaemia in group 1 (10 +/- 1.2%/g tissue). MDP injection restored the Kupffer cell activity (30.6 +/- 3.22%/g tissue) while dextran sulphate and gadolinium chloride administration markedly decreased SRBC 51Cr liver uptake. Our findings demonstrate that MDP in able to protect the liver from ischaemic insult while blockade of Kupffer cells was deleterious in rats subjected to liver ischaemia.