Increases in Cathepsins B and L and Thiol Proteinase Inhibitor in Muscle of Dystrophic Hamsters. Their Localization in Invading Phagocytes

Abstract

In dystrophic hamsters, increases in the levels of cathepsin B plus L and thiol proteinase inhibitor were marked in skeletal muscle, but only slight in heart muscle. The lysosomal hydrolases did not increase in parallel in dystrophic muscle: cathepsin B plus L and β-glucuronidase increased, but cathepsin C and acid phosphatase did not. In immunohistochemical studies with antibodies against rat liver cathepsin B and thiol proteinase inhibitor, the proteinase and inhibitor were both stained in phagocytes, chiefly macrophages, but not in muscle cells, indicating that the increases in cathepsin B plus L and thiol proteinase inhibitor in dystrophic muscle are due to their presence in invading phagocytes. The levels of cathepsin B plus L, β-glucuronidase and thiol proteinase inhibitor in isolated peritoneal macrophages were 50 to 180 times higher than those in skeletal muscle, but the levels of acid phosphatase and cathepsin C were only about 10 to 30 times those in skeletal muscle. Plots of the cathepsin B plus L activities versus the level of thiol proteinase inhibitor in homogenates of tissues of various animals showed an exponential rather than a linear relation between the two activities, suggesting that the syntheses of the proteinases are higher than that of the inhibitor in phagocytes invading dystrophic muscle.