Effects of chloroquine on lysosomes and endocytosis by liver cells in vivo.

1. Chloroquine accumulation in rat liver after a single and repeated drug administration and lysosomal changes resembling some symptoms of lysosomal storage diseases were observed. 2. Repeated chloroquine treatment of rats resulted in increased activity of liver lysosomal enzymes acid phosphatase and beta-galactosidase and a significant enhancement of the activities of cathepsin D and cysteine proteinases were found. 3. No changes in the activity of liver macrophages (as assessed by the colloidal carbon clearance test) or in fluid-phase endocytosis of the marker 125I-polyvinyl-pyrrolidone by hepatocytes in vivo were found.

Endocytosis by liver cells during suppression of intralysosomal proteolysis.

The lysosomotropic agent chloroquine is widely used as a specific inhibitor of intralysosomal proteolysis in isolated hepatocytes. It was shown that in vitro chloroquine reversibly inhibited purified cathepsins H, B, L in concentrations less than those observed inside lysosomes in vivo. However, administration of high doses of chloroquine to rats (30-50 mg/kg i.p. as a single or repeated injections) was followed by increased cathepsin D and cysteine proteinase activities, as well as other lysosomal enzymes. Chloroquine administration did not induce any changes of carbon particles phagocytosis by liver cells (macrophages); modifications of fluid-phase (125I-PVP uptake) and receptor-mediated endocytosis (125I-asialo-fetuin uptake) were noted. Chloroquine administered in vivo reproduced some symptoms of lysosomal storage diseases (especially during repeated drug administration).

Liver and serum lysosomal enzymes activity during zymosan-induced inflammation in mice.

Liver and serum lysosomal enzymes (acid glucosidases and cysteine proteinases) during zymosan-induced stimulation of MPS or MPR depression induced by GdCl3 have been studied. Zymosan was used as a model for study of inflammation in vivo. The development of inflammation induced by zymosan was followed by increase activity of macrophage activation markers - beta-N-acetylglucosaminidase (NAGlu) and beta-N-acetylgalactosaminidase (NAGal) in liver and serum. There was enhance of liver cysteine proteinases activity. Similar, less prominent (partly) data were obtained during macrophage depression induced by GdCl3.

[Endocytosis by liver cells during stimulation of the mononuclear phagocyte system by yeast polysaccharides]. / Endotsitoz kletkami pecheni pri stimuliatsii sistemy mononuklearnykh fagotsitov drozhzhevymi polisakharidami.

Endocytosis (phagocytosis, fluid-phase- and receptor-mediated endocytosis) by liver cells, lysosomal enzyme activities have been studied during macrophages stimulation by yeast polysaccharides. It was shown that like macrophages stimulator zymosan, yeast polysaccharides cryelan and rhodexman increased the carbon particles phagocytosis. The most effective was intravenous administration of yeast polysaccharides. Compared to rhodexman, the effect of cryelan was more prominent. Macrophages stimulation was followed by suppression of fluid-phase endocytosis by liver cells. Increased activity of cathepsin B was discovered on day 5 after macrophages stimulation (proteinase, most typical for macrophages enzymes).