Elastin peptides elicited during acute lung inflammation detected in gall bladder by elastase-sensitive Overhauser-enhanced MRI

Lung inflammation diseases are a huge burden worldwide because they lead to life-threatening lung function impairment. Lung structure degradation occurs mainly through neutrophil elastase (NE) unchecked activity. Currently, irreversible damages can be diagnosed only after long and silent lung structural degradation occurred. Thus, a non-invasive diagnostic method detecting elastase activity in the lungs would provide early diagnosis and treatments. Here nitroxide-labeled elastin fragments were used as NE substrate to produce elastin-derived peptides (EDPs) that generate contrast with Overhauser-enhanced Magnetic Resonance Imaging. Labeled elastin was instilled in the lung of mice with LPS-induced acute lung inflammation whereas pre-digested elastin was administered in control mice. Lung imaging revealed that the elastin-based contrast agent indeed unveiled lung inflammation yielding, with however a poor contrast and a poor reproducibility. Unexpectedly, this experiment led to the observation that nitroxide-labeled EDPs elicited in the lungs of inflammatory mice or in positive control mice generated high contrasts in the gallbladder where they accumulated. This suggests a very efficient capture and transport of these peptides by liver cells. Since elastin-derived peptides have been associated to nonalcoholic steatohepatitis (NASH) it strengthens the idea of a potential link between chronic lung inflammation diseases like COPD or cystic fibrosis and NASH.