Endocytosis by Liver Cells During Suppression of Intralysosomal Proteolysis

Abstract

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 ( 125 I-PVP uptake) and receptor-mediated endocytosis ( 125 I-asialo-fetuin uptake) were noted. Chloroquine administered in vivo reproduced some symptoms of lysosomal storage diseases (especially during repeated drug administration).

From blood to brain: amoeboid microglial cell, a nascent macrophage and its functions in developing brain

“…It also reduces the expression of MHC II on Kupffer cells [99] . Besides its anti-inflammatory actions, chloroquine inhibits lysosomal degradation and produces lysosomal changes resembling that of lysosomal storage disease in a variety of cells, including macrophages [100,101] . Increased vacuolation and the accumulation of lysosomes were observed in AMC in response to the intraperitoneal administration of chloroquine in 1-d-old rats.…”

Lysosomotropic Features and Autophagy Modulators among Medical Drugs: Evaluation of Their Role in Pathologies

“…According to Mauthe et al [52], this drug inhibits autophagic flux by decreasing autophagosome-lysosome fusion. It was demonstrated in vitro that CQ reversibly inhibits purified cathepsins H (CH), B (CB), and L (CL) at concentrations less than those observed inside lysosomes in vivo [53]. Chloroquine administration did not induce any changes of carbon particle phagocytosis by liver macrophages, modifications of fluid-phase ( 125 I-PVP) uptake, and receptor-mediated endocytosis ( 125 I-asialo-fetuin uptake).…”

A comparative study of the hypolipidaemic effects of a new polysaccharide, mannan Candida albicans serotype A, and atorvastatin in mice with poloxamer 407-induced hyperlipidaemia

“…Mannan, which belongs to a class of immunomodulators of polysaccharide origin, has been shown to stimulate macrophages in vivo through its interaction with the mannose receptor . Polysaccharides, unlike statins, are natural stimulators of macrophages, which cause the macrophages to increase their endocytic activity . Following endocytosis, these branched polysaccharides have the capacity to activate LDL and scavenger receptors and increase the uptake of atherogenic LDL cholesterol, as well as other lipoproteins with modified chemical structures.…”

“…[9][10][11][12] Polysaccharides, unlike statins, are natural stimulators of macrophages, which cause the macrophages to increase their endocytic activity. [13,14] Following endocytosis, these branched polysaccharides have the capacity to activate LDL and scavenger receptors and increase the uptake of atherogenic LDL cholesterol, as well as other lipoproteins with modified chemical structures. It has also been suggested that excess cholesterol may potentially be removed from the atherosclerotic plaque by the activated macrophages.…”