MECHANISM OF COLLAGEN NETWORK STABILIZATION IN HUMAN IRREVERSIBLE GRANULOMATOUS LIVER FIBROSIS

Background & Aims: Cross-linking participates in the increased stabili ty of collagen towards proteolytic degradation. Liver collagen cross-l inking by pyridinoline, from the lysyl oxidase pathway, and by pentosi dine, issued from glycation, was investigated to determine their respe ctive contribution to collagen stabilization in patients with an irrev ersible liver fibrosis caused by the parasitic granulomatous disease a lveolar echinococcosis. Method: Liver pyridinoline and pentosidine wer e analyzed by high-performance liquid chromatography, and urinary pyri dinoline was analyzed by immunoassay. Cross-linked type 1 collagen was localized by immunohistochemistry with an antibody against. the C-ter minal part of the molecule, involved in pyridinoline formation, that w as measured in serum by radioimmunoassay. Results: In contrast to pyri dinoline, pentosidine decreased in fibrotic lesions. Cross-linked type I collagen was located predominantly in collagen bundles in the perip arasitic granuloma. Serum pentosidine and urinary pyridinoline levels did not differ significantly from controls, but the serum concentratio n of the C-terminal telopeptide of type I collagen increased significa ntly. Conclusions: Lysyl oxidase-mediated cross-linking is the major p rocess contributing to the stabilization of collagen in granulomatous fibrosis, and glycation is not significantly involved in it. The chang es induced by alveolar echinococcosis in liver collagen metabolism are associated with an increase in serum C-telopeptide of type 1 collagen .