In vitro induction of lysosomal enzymes by phagocytosis.
The in vitro induction of lysosomal enzymes by phagocytosis was demonstrated in cultivated mouse peritoneal macrophages. The contribution of each of several steps in the endocytic process to enzyme induction was examined. The enzymatic response after the uptake of equal numbers of erythrocytes (RBC) and nondigestible particles were compared. Phagocytosis of RBC produced a marked increase in the levels of acid phosphatase, beta-glucuronidase, and cathepsin D. Puromycin (1 microg/ml) inhibited the enzyme response. In contrast, phagocytosis of polyvinyl toluene, polystyrene, and insoluble starch particles produced no increase in macrophage lysosomal enzymes, although fusion of phagosomes with preexisting lysosomes occurred normally. The endocytic stimulus to synthesis of inducible lysosomal enzymes, therefore, occurred at or beyond the stage of digestion. Purified protein (bovine gamma globulin) aggregates and homopolymer coacervates of poly-l-glutamic acid: poly-l-lysine were effective inducers of lysosomal acid phosphatase, beta-glucuronidase, and cathepsin D, whereas homopolymers of the same D-amino acids were ineffective as inducers. Both the quantity of phagocytized substrate and its rate of enzymatic hydrolysis appear to control the level and persistance of lysosomal hydrolases.
D000135:Acid Phosphatase / Q000032:analysis / Q000096:biosynthesis*; D000818:Animals; D002403:Cathepsins / Q000032:analysis / Q000096:biosynthesis*; D046508:Culture Techniques; D004790:Enzyme Induction; D004912:Erythrocytes; D005966:Glucuronidase / Q000032:analysis / Q000096:biosynthesis*; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology*; D008264:Macrophages / Q000201:enzymology*; D051379:Mice; D008854:Microscopy, Electron; D009163:Mycobacterium bovis; D010587:Phagocytosis; D010873:Pinocytosis; D011137:Polystyrenes / Q000494:pharmacology; D011145:Polyvinyls / Q000494:pharmacology; D011506:Proteins / Q000032:analysis; D011691:Puromycin / Q000494:pharmacology; D012756:Sheep; D013213:Starch / Q000032:analysis; D014050:Toluene / Q000494:pharmacology
D011137:Polystyrenes; D011145:Polyvinyls; D011506:Proteins; D014050:Toluene; D011691:Puromycin; D013213:Starch; D000135:Acid Phosphatase; D005966:Glucuronidase; D002403:Cathepsins