Abstract
Introduction Desmosine and isodesmosine (DID) are biomarkers for elastic fibre damage in pulmonary emphysema. However, current methods for measuring lung DID involve tissue hydrolysis and lack specificity for those fibres undergoing breakdown. To address this limitation, free (nonpeptide-bound) DID content in unhydrolyzed tissues was evaluated as a more accurate biomarker in an animal model of pulmonary emphysema. Methods Hamsters were treated with either cigarette smoke and lipopolysaccharide (LPS), room air and LPS, or room air alone (controls). Free DID levels in fresh and formalin-fixed lungs were measured by LC-MS/MS and correlated with the mean linear intercept (MLI) measure of airspace size. Results There was no significant difference in free DID between fresh and formalin-fixed lungs. Animals treated with smoke and LPS had significantly higher levels of free DID than the LPS only group (359 vs. 93.1 ng/g wet lung, respectively; p = 0.0012) and room air controls (undetectable levels; p = 0.0002). There was a significant positive correlation between free DID and MLI (p < 0.0001). Conclusions The results support the hypothesis that free lung DID is a sensitive indicator of alveolar wall injury that may be used to study the development of pulmonary emphysema in both animal models and post-mortem human lung tissue.
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