Degradation of elastin in experimental elastase-induced emphysema measured by a radioimmunoassay for desmosine.

Experimental emphysema, produced by a single intratracheal injection of elastase in hamsters, progresses in severity over months. To investigate whether this progression is due to continuous elastolysis, we measured the urinary excretion of desmosine by radioimmunoassay (RIA) as a measure of elastin catabolism in vivo. Normal hamster excreted 1.6 microgram of desmosine, equivalent to a daily turnover of approximately 0.4 mg of elastin. During the first 24 hr after injection of 25 units of elastase, excretion of desmosine was increased threefold, rapidly returning to normal over several days. Desmosine excretion was normal after 6 days. Homogenates of lungs from elastase-injected hamsters were incubated in vitro, and the release of soluble desmosine was followed by RIA as a measure of the active elastase in the tissue. The method was sufficiently sensitive to detect 0.1 microgram of enzyme bound to elastin. Desmosine solubilized in vitro from lungs removed at intervals after elastase injection was 10-fold that of control at 1 hr and slightly elevated at 48 hr, but equaled control levels at 7 days. These results indicate that the late progression of elastase-induced emphysema is not accompanied by increased elastolysis.

The induction of emphysema with elastase. II. Changes in connective tissue.

Both clinical and experimental evidence implicate proteolytic enzymes active against elastin in the pathogenesis of emphysema. Paradoxically, however, the elastin content of emphysematous human lungs at autopsy has been normal. When emphysema was produced in hamsters by a single intratracheal injection of 25 units of porcine pancreatic elastase, the elastin content of the lungs was reduced from 1.40 +/- 0.22 mg. in controls to 0.43 +/- 0.10 mg. 24 hours after injection, and histologic sections showed that many elastic fibers had disappeared. The elastin content of the lungs gradually increased, approaching normal values by 2 months after injection. The incorporation of 14C-proline into elastin was markedly elevated during the first 2 weeks after injection, decreasing nearly to normal by 2 months. The synthesis of collagen was also increased, indicated by an increase in the collagen content of the lung, an increase in the prolyl hydroxylase activity, and an increase in incorporation of labeled proline into collagen. During the period of active resynthesis of elastin, small clumps of microfibrils and elastic fibrils were visible by electron microscopy within grooves on the surface of septal connective tissue cells in the lungs. Many elastic fibers seen in histologic sections up to 4 months after injection were of abnormal configuration and disorganized.