The kinetics of elastolysis: elastin catabolism during experimentally induced fibrosis.
Lung injury and matrix destruction result in the release into the circulation of desmosine, a product of elastin catabolism. To determine whether measurements of desmosine concentrations in the urine can provide important information about the severity of lung injury, we measured the kinetics of lung elastin catabolism following elastase-induced and fibrotic lung injury in mice. Pancreatic elastase instillation in the lung caused immediate elastin destruction, removing as much as 25% of the lung elastin within the first few hours. Peak concentrations of desmosine peptides appeared in the blood within 1-2 hours, and soluble elastin peptides in the lung and urine followed a similar course with peak levels occurring early and then declining rapidly, approaching control levels by 24 hours. More than half of the desmosine peptides removed from the lung following elastase injury were sequestered by the kidney and then slowly released over a period of several days. Lung histology and morphological measurements indicated that bleomycin, TiO2, and SiO2 instillation resulted in severely fibrotic lungs. However, the lung injuries sustained from these agents resulted in minimal elastin damage, representing less than 0.1% of the total lung elastin catabolized as estimated by desmosine analysis. The rapid accumulation of desmosine in renal tissue and its slow release into the urine keep urine concentrations low and minimize the power of urine desmosine assays for quantifying low level tissue destruction.
Starcher
B
B
Department of Biochemistry, University of Texas Health Center-Tyler 75710, USA.
Peterson
B
B
D000818:Animals; D001761:Bleomycin / Q000633:toxicity; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003895:Desmosine / Q000032:analysis / Q000378:metabolism; D004195:Disease Models, Animal; D004549:Elastin / Q000378:metabolism*; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D010196:Pancreatic Elastase / Q000633:toxicity; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D012822:Silicon Dioxide / Q000633:toxicity; D013997:Time Factors; D014018:Tissue Distribution; D014025:Titanium / Q000633:toxicity
D003895:Desmosine; D001761:Bleomycin; C009495:titanium dioxide; D012822:Silicon Dioxide; D004549:Elastin; D014025:Titanium; D010196:Pancreatic Elastase