Lung collagen cross-links in rats with experimentally induced pulmonary fibrosis

Joan E. Gerriets, Karen M. Reiser, Jerold A Last

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18 Scopus citations


Rats were intratracheally instilled with bleomycin or with silica (quartz) dust to induce lung fibrosis. Several weeks later, purified collagen chains (or collagen digests) were isolated from the lungs of these animals and from age-matched controls instilled intratracheally with saline solution, and the ratios of hydroxylysine to lysine and of the difunctional cross-links DHLNL to HLNL were quantified. Collagen from fibrotic lungs had significantly higher ratios of DHLNL:HLNL than did control lungs, 15.5 ± 4.8 and 17.1 ± 4.8 vs. 2.3 ± 0.5 for the silica-instilled and the bleomycin-instilled animals, respectively. The hydroxylysine:lysine ratio was significantly increased for the α1(I) chain, to a value 170% of that of lung collagen from control animals, and for several of its constituent CNBr peptides. Lung tissue was exhaustively digested with collagenase and specific cross-linked peptides were isolated and characterized. The cross-linked α1(I) x α1(I) peptide linked by the residues 87 x 16(C), with a ratio of DHLNL:HLNL of 17:1, demonstrated that the increased hydroxylation of the difunctional cross-links in fibrotic lung collagen could be accounted for in past by increased hydroxylation of the lysine residue at position 16(C) of the C-terminal telopeptide of the collagen α1(I) chain. It proved impossible to locate the corresponding N-terminal cross-linked fragment from α1(I) x α1(I) chains, 9(N) x 930, possibly due to further reactions of this material to form the material referred to as poly(CB6). Isolated poly(CB6) accounted for more than half of the total α1(I)CB6 peptide expected in lung collagen, and had a hydroxylysine:lysine content 2.8 times greater in bleomycin-treated animals than in their age-matched controls. Evidence was also found for a cross-linked α1(III) x α1(I) peptide linking residue 87 from the α1(III) chain with residue 16(C) from the α1(I) chain; it also had an increased ratio of DHLNL:HLNL. We conclude that the increased hydroxylation of lysine observed in two different animal models of lung fibrosis occurs preferentially at the N- and C-terminal nonhelical extension peptides of the α1(I) collagen chains, and that this apparent specificity of overhydroxylation of fibrotic collagen may have important structural and pathological consequences.

Original languageEnglish (US)
Pages (from-to)121-131
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Issue number2
StatePublished - Jun 7 1996


  • Bleomycin
  • Collagen
  • Collagen cross-linking
  • Fibrosis
  • Hydroxylysine

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Biophysics


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