Under steady state conditions the intracellular pathway is the major route of collagen catabolism in tissues characterised by rapid collagen turnover. In the lung, the collagen is subject to continuous remodelling and turnover however, the intracellular pathway of collagen degradation is unusual under physiological conditions.

The current authors previously described crystalloid inclusions in alveolar macrophages of mice with genetic emphysema at the time of septal disruption. Using an immunogold technique these inclusions were identified as collagen-derived products and related to intracytoplasmic collagen degradation. To examine whether a different degree of protease burden in lung interstitium may influence the route of intracellular collagen degradation, collagen phagocytosis by alveolar macrophages was studied in various mouse models of emphysema at the time when emphysema develops.

Evident collagen by-products in alveolar macrophages were observed in destructive processes characterising spontaneous models of emphysema either with negligible (blotchy mouse) or moderate (pallid mouse) elastase burden. On the other hand, intracellular collagen by-products were appreciated only in a few macrophages from tight-skin mice with high elastolytic burden and could not be observed in mice with a very severe burden after elastase instillation. In conclusion, the interstitial level of proteases burden can affect the way by which the collagen is cleared (intracellularly versus extracellularly).