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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.

Degradation of elastin was studied in rats after intraperitoneal implantation of a suspension of 14C-elastin that had been prepared by labeling bovine elastin with 14C-formaldehyde. Most of the degradation of 14C-elastin, measured by releasing the radioactivity in urine and feces, occurred between 6 and 15 days after the implantation. During this period an increase of leukocytes and macrophages in the implanted site was observed. This followed a brief increase in neutrophils. Furthermore, an elevation of the elastolytic activity, measured by the 14C-elastin, was found in cell lysates of both macrophages and neutrophils, which were recovered by lavage of the peritoneal cavity. But the enzymatic activity was not found in the cell-free lavage. On the contrary, there was elastase inhibitor in the lavage, increased by the implantation. The mechanism of the elastin degradation in the peritoneal cavity was discussed.