Contribution of complement-stimulated hepatic macrophages and neutrophils to endotoxin-induced liver injury in rats

✍ Scribed by Dr. Hartmut Jaeschke; Anwar Farhood; C. Wayne Smith

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 801 KB
• Volume: 19
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840190424

✦ Synopsis

The role of complement as potential activator for tissue macrophages and neutrophils was investigated in an experimental model of endotoxin-induced liver hjury in male Fischer rats. Iqjection of SaZmoneUa enteritidis endotoxin (1 mg/kg) into Corynebacterium purvum-pretreated animals (7 mg/kg, single dose 6 days before endotoxin) resulted in severe oxidant stress, as indicated by a 37-fold increase of plasma levels of glutathione disulfide (basal concentration, 0.36 2 14 pmol/L), accumulation of neutrophils in the liver (600 f 31 neutrophile/SO high-power fields) and liver injury (plasma ALT, 1184 It 185 Un; necrosis; 19% 2 3%) 10 hr after endotoxin. The oxidant stress i n d u d by 1 mg/kg endotoxin in the C. parvum-treated animals was always sigd%cantly higher than that in control animals receiving the same dose of endotoxin. Inhibition of complement activation with the soluble complement receptor type 1 attenuated the oxidant stress and liver iqjury by 60% to 65% but had no effect on hepatic neutrophil accumulation or plasma tumor necrosis factor-a levels. Treatment with a monoclonal antibody directed against the a-chain of CDllb/CDlS adhesion proteins (clone 17), which was highly effective in attenuating ischemia-reperfusion injury in the liver by reducing the number of neutrophils and functionally inactivating these cells, neither protected against parenchymal cell injury nor affected hepatic neutrophil infiltration in the C. parvum model. We conclude that reactive oxygen derived from complement-stimulated macrophages is critical for the development of liver bjury in the C. parvumlendotoxin model. (HEPATOLOGY 1994;19973-979.) Corynebacterium parvumlendotoxin is a widely used experimental model of endotoxin-induced liver injury.

Pretreatment with C. parvum causes recruitment of macrophages into the liver (1). These macrophages are