Degradation of rat lung collagens by cathepsin B.
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.
Cardozo
C
C
Department of Medicine, Mount Sinai School of Medicine, New York, New York.
Kurtz
C
C
Lesser
M
M
D000818:Animals; D002401:Cathepsin B / Q000494:pharmacology*; D002478:Cells, Cultured; D003094:Collagen / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D003470:Culture Media / Q000737:chemistry; D006909:Hydroxyproline / Q000032:analysis; D008168:Lung / Q000737:chemistry / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D003470:Culture Media; D003094:Collagen; D002401:Cathepsin B; D006909:Hydroxyproline