[Regulation of liver cysteine proteinases during macrophagal stimulation and depression]

The lysosomal pathway of intracellular protein degradation involves the cooperative action of proteinases, among which cysteine proteinases cathepsin B and cathepsin L are particularly important. The hypothesis that the abnormal ratio of proteinases/proteinase inhibitors (i.e. higher activities of proteinases and lower activities of their inhibitors) results in uncontrolled proteolysis and cellular dysfunctions has been experimentally tested. Cathepsin B was used as a marker of macrophagal lysosomes and cathepsin L was employed as a marker of hepatocytic lysosomes. Zymosan stimulation of macrophages was shown to induce increased secretion of macrophagal lysosomal enzymes into blood during early zymosan administration, followed by higher rates of phagocytosis and labilization of lysosomes both of macrophages and hepatocytes labilization. Macrophagal depression induced by gadolinium chloride in rats was also accompanied by increased secretion of acid hydrolases into blood and labilization of macrophageal lysosomes, which reflects the lysosomotropic properties of the agent. Gadolinium chloride prevented zymosan stimulation of macrophages in the liver, but not in the spleen and lung. A new approach is proposed to evaluate the functional activity of hepatocytic lysosomes by the marker lysosomal enzymes of macrophages (cathepsin B) and hepatocytes (cathepsin L). Possible modes of regulation of endogenous proteinases are considered with special emphasis on the protective function of endogenous proteinase inhibitors secreted by macrophages simultaneously with cathepsin B and other cysteine proteinases.