The effect of chloroquine on lysosomal function and cell-coat glycoprotein transport in the absorptive cells of cultured human small-intestinal tissue.
The effect of chloroquine, an inhibitor of intralysosomal catabolism, on the synthesis, transport, and degradation of cell-coat glycoproteins in absorptive cells of cultured human small-intestine tissue was investigated by morphometrical, autoradiographical, and biochemical methods. Neither synthesis nor transport of cell-coat material was affected by the drug, but culturing of the absorptive cells in the presence of chloroquine led to a dose- and time-dependent enlargement of the dense bodies; other cell structures showed no alterations. 3H-fucose-labelled material accumulated in the dense bodies of the absorptive cells of these cultures. Since no increase of beta-glucuronidase and acid phosphatase activity (both lysosomal enzymes of glycoprotein nature) was found, this accumulation of radiolabeled material can be explained as a chloroquine-mediated inhibition of the degradation of cell-coat glycoproteins. These macromolecules probably enter the lysosome-like bodies by a crino-phagic mechanism, i.e., fusion of these organelles with the apical vesicles and tubules involved in intracellular transport. These findings suggest that the lysosome-like bodies have a function in the regulating of cell-coat glycoprotein transport in human intestinal absorptive cell, i.e., the degradation of excess cell-coat material.
D001692:Biological Transport / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D006867:Hydrolases / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000648:ultrastructure; D007421:Intestine, Small; D008247:Lysosomes / Q000378:metabolism* / Q000648:ultrastructure; D009924:Organ Culture Techniques; D009940:Organoids / Q000648:ultrastructure; D013997:Time Factors
D006023:Glycoproteins; D002738:Chloroquine; D006867:Hydrolases