Hepatic metabolism of colloidal gold-low-density lipoprotein complexes in the rat: evidence for bulk excretion of lysosomal contents into bile.

Rats were treated with 17 alpha-ethinyl estradiol to induce high levels of low-density lipoprotein receptors in hepatocytes. When these rats were given intravenous injections of low-density lipoprotein-colloidal gold complexes, most of the gold (labeled with 195Au) appeared to be taken up by Kupffer cells, as were complexes of colloidal gold with albumin or polyvinylpyrrolidone. However, when these rats were also administered gadolinium chloride, which blocks Kupffer cell activity, most of the low-density lipoprotein-gold (but not gold complexed with albumin or polyvinylpyrrolidone) was taken up into hepatocytes by receptor-mediated endocytosis and concentrated in peribiliary lysosomes, as determined by electron microscopy. Colloidal gold taken up as a complex with low-density lipoprotein was excreted into the feces via the common bile duct at a maximal rate of about 5% daily, 4 to 12 days after injection. Thereafter, the rate of gold excretion fell off until reaching a plateau after 3 weeks. At this late time, most of the colloidal gold was shown by electron microscopy to be in Kupffer cells, whereas earlier (6 days after injection) it was contained mainly in older hepatocytic lysosomes, identified by lipofuscin granules. It is concluded that, in rats, hepatocytic lysosomes empty most of their contents into bile every week or two, apparently by exocytosis.