Mechanism of collagen network stabilization in human irreversible granulomatous liver fibrosis.
OBJECTIVE
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.
Ricard-Blum
S
S
Centre National de la Recherche Scientifique Unité de Recherche Associée 1459, Institut Pasteur de Lyon, Lyon, France.
Bresson-Hadni
S
S
Guerret
S
S
Grenard
P
P
Volle
P J
PJ
Risteli
L
L
Grimaud
J A
JA
Vuitton
D A
DA
D000596:Amino Acids / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003094:Collagen / Q000378:metabolism*; D004444:Echinococcosis, Hepatic / Q000378:metabolism; D006031:Glycosylation; D006099:Granuloma / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000378:metabolism*; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008249:Protein-Lysine 6-Oxidase / Q000378:metabolism; D011863:Radioimmunoassay
D000596:Amino Acids; C015484:pyridinoline; D003094:Collagen; D001120:Arginine; C062187:pentosidine; D008249:Protein-Lysine 6-Oxidase; D008239:Lysine