Mechanism of collagen network stabilization in human irreversible granulomatous liver fibrosis

Gastroenterology. 1996 Jul;111(1):172-82. doi: 10.1053/gast.1996.v111.pm8698196.


Background & aims: Cross-linking participates in the increased stability of collagen towards proteolytic degradation. Liver collagen cross-linking by pyridinoline, from the lysyl oxidase pathway, and by pentosidine, issued from glycation, was investigated to determine their respective contribution to collagen stabilization in patients with an irreversible liver fibrosis caused by the parasitic granulomatous disease alveolar echinococcosis.

Methods: Liver pyridinoline and pentosidine were analyzed by high-performance liquid chromatography, and urinary pyridinoline was analyzed by immunoassay. Cross-linked type I collagen was localized by immunohistochemistry with an antibody against the C-terminal part of the molecule, involved in pyridinoline formation, that was measured in serum by radioimmunoassay.

Results: In contrast to pyridinoline, pentosidine decreased in fibrotic lesions. Cross-linked I collagen was located predominantly in collagen bundles in the periparasitic granuloma. Serum pentosidine and urinary pyridinoline levels did not differ significantly from controls, but the serum concentration of the C-terminal telopeptide of type I collagen increased significantly.

Conclusions: Lysyl oxidase-mediated cross-linking is the major process contributing to the stabilization of collagen in granulomatous fibrosis, and glycation is not significantly involved in it. The changes induced by alveolar echinococcosis in liver collagen metabolism are associated with an increase in serum C-telopeptide of type I collagen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / metabolism
  • Arginine / analogs & derivatives
  • Arginine / metabolism
  • Chromatography, High Pressure Liquid
  • Collagen / metabolism*
  • Echinococcosis, Hepatic / metabolism
  • Glycosylation
  • Granuloma / metabolism*
  • Humans
  • Immunohistochemistry
  • Liver / metabolism*
  • Liver Cirrhosis / metabolism*
  • Lysine / analogs & derivatives
  • Lysine / metabolism
  • Protein-Lysine 6-Oxidase / metabolism
  • Radioimmunoassay


  • Amino Acids
  • pyridinoline
  • Collagen
  • Arginine
  • pentosidine
  • Protein-Lysine 6-Oxidase
  • Lysine