Collagen cross-linking in adult patients with acute and chronic fibrotic lung disease. Molecular markers for fibrotic collagen.

Lung tissue from patients with interstitial lung disease (ILD), adult respiratory distress syndrome (ARDS), and control subjects with no obvious fibrotic lung disease was analyzed for its content of the collagen cross-links hydroxylysinonorleucine (HLNL), dihydroxylysinonorleucine (DHLNL), and hydroxypyridinium (OHP). We observed significant elevations of the DHLNL:HLNL ratio in patients with ARDS, and significant increases in the content of OHP in lungs of patients with ILD. These results are consistent with data from animal models of fibrotic lung disease, suggesting that increases in the DHLNL:HLNL ratio of lung collagen may serve as a marker of an acute fibrotic episode, whereas increased lung collagen OHP content serves as a marker of chronic lung fibrosis. We suggest that the underlying mechanism for the changes in DHLNL content in (pre)fibrotic acutely injured lung tissue and in OHP content in long-term fibrosis may be an increase in the activity of lysyl hydroxylase, a key intracellular enzyme responsible for a specific post-translational modification of collagen.