Degradation of rat lung collagens by cathepsin B

Abstract

The lysosomal proteinase cathepsin B degrades purified insoluble collagen in vitro. To determine whether the enzyme degrades collagens present in normal extracellular matrices, we quantitated release of hydroxyproline-containing peptides during incubation of rat lung explants with bovine spleen cathepsin B. Incubation of explants with cathepsin B at pH 5.9 caused significant release of hydroxyproline, indicating collagen degradation, without apparent injury to lung parenchymal cells, as determined by release of lactate dehydrogenase. Release of hydroxyproline was completely inhibited by E-64, a specific inhibitor of cysteine proteinases. Cathepsin B demonstrated significant collagenolytic activity over a range of pH values from 4.0 to 6.5. Little activity was present at pH 7.0 or above. The findings indicate that cathepsin B is capable of degrading collagens embedded in the complex extracellular matrix of the lung and suggest that the enzyme may contribute to collagen degradation in vivo.