Kupffer cell depletion associated with capillarization of liver sinusoids in carbon tetrachloride-induced rat liver cirrhosis

Rats were made cirrhotic by carbon tetrachloride inhalation associated with phenobarbital in the drinking water over 10 weeks. After a 1-week recovery period a 99mTc sulphur colloid radioisotope scan of the liver was carried out on each animal following bolus injection into the iliac vein. Kupffer cells were then histologically identified by one of three methods: colloidal carbon uptake, iron staining after ferritin-dextran, or endogenous peroxidase staining. The degree of liver injury was classified into four pathological groups and these were correlated with the phagocytic capacity of each liver as recorded on the isotope scan. All three histological markers demonstrated that in normal liver, Kupffer cells are more plentiful in periportal areas. In cirrhotic liver, there were very few Kupffer cells in nodular regenerative areas, where continuous capillaries are found, but Kupffer cells were present in the remaining more normal trabecular-sinusoidal areas. Morphometric counting of carbon- and ferritin-labelled Kupffer cells demonstrated a significant decrease in cirrhotic livers. A close correlation was also found between increasing degree of liver injury and diminished hepatic phagocytic capacity, as demonstrated by the radioisotope scan. The study demonstrates that where regenerative liver is capillarized, with replacement of fenestrated sinusoids, Kupffer cells are absent.