Hepatocyte contribution to hepatic collagen production in uiuo was estimated in rats, based on the fact that ornithine is used for protein synthesis in the liver as arginine after conversion by way of the urea cycle only by hepatocytes. From rats given a mixture of [ 14C] ornithine and [SH]arginine, hepatic collagen and serum albumin were obtained. The hepatocyte contribution was calculated from the I4C and SH in arginine purified from collagen and albumin by high performance liquid chromatography. The contribution was less than 10% of total collagen production in normal and early fibrotic livers induced by a single dose of carbon tetrachloride or dimethylnitrosamine. We conclude that hepatocytes may play a minor role in collagen production in normal and early fibrotic rat livers. (HFPATOLOGY 1991; 14:361-367.)
Because hepatocytes and nonparenchymal cells can synthesize collagen in v h -0 ( 1 -l l ) , it is a matter of interest which cells contribute to collagen production in the liver.
Chojkier (12) devised a method for assessing the hepatocyte contribution to in vivo hepatic collagen production and reported that most of hepatic collagen was synthesized by hepatocytes in normal liver. The principle of this method is that the contribution can be calculated from labeled proline( + hydroxyproline) and arginine in hepatic collagen and proteins exclusively produced by hepatocytes such as albumin and transferrin after administration of dual-labeled proline and ornithine because ornithine can be incorporated into proteins as arginine converted by way of the urea cycle only in hepatocytes in the liver.
Although this method is theoretically excellent, several points in his procedures need improvement.
First, large amounts of newly synthesized collagen might be lost in his purification procedure. Second, the relative contents of proline to arginine in albumin and collagen molecules are taken into account in the calculation of hepatocyte contribution, whereas the contents of proline( + hydroxyproline) in collagen differ de-