Colchicine effects on lysosomal enzyme induction and intracellular degradation in the cultivated macrophage.

Abstract

The effects of colchicine on lysosomal fusion and lysosomal enzyme induction in the cultivated mouse peritoneal macrophage have been examined. Colchicine (10- minus 6 M), but not lumicolchicine, inhibited lysosomal enzyme induction by both phagocytic and pinocytic stimuli. In addition, the drug significantly retarded pinocytic uptake of [3-H] sucrose and transport of the amino acids [3-H] alpha aminoisobutyric acid and L-[3-H] leucine. In contrast, lumicolchicine had no effect on pinocytosis or amino acid transport. Thus, a role for intact microtubules in lysosomal enzyme induction, pinocytosis, and amino acid uptake in these cells is suggested. That colchicine inhibited lysosomal enzyme induction by phagocytic stimuli under conditions in which pinocytosis contributed little to the enzyme rise indicated that inhibition of pinocytosis was unlikely to account for colchicine effects on lysosomal enzyme induction. Effects of colchicine on degradation of phagocytized and pinocytized substrates were examined to determine if intact microtubules are required for fusion among lysosomes, pinosomes, and phagosomes. Colchicine did not alter the rate of intracellular digestion of radiolabeled bacteria by the cultivated macrophage. Similarly, it had no effect on enzymatic hydrolysis of intracellular [3-H] sucrose resulting from uptake of exogenous invertase. The finding that colchicine had no effect on the functional consequences of fusion of lysosomes with endosomes suggests that intact microtubules are not required for fusion among these constituents of the vacuolar apparatus.

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

“…It has been hypothesized that microtubules are important for the secretion of lysosomal enzymes and the intracellular degradation of materials phagocytosed by macrophages [107] . It has also been suggested that microtubules are necessary for the fusion of lysosomes with endosomes which must precede intracellular digestion of phagocytosed materials [108] , whereas others have reported that intact microtubules are not required for the lysosomal-endosomal fusion [109] . We found that the mitotic activity of AMC was suppressed by colchicine, but the phagocytic activity remained unaffected [103] .…”

Secretion of macrophage neutral proteinase is enhanced by colchicine.

“…Colchicine has little effect for several hours on total protein synthesis in the macrophage (16), but the species formed could be substantially modified in the presence of colchicine (13). The continued accumulation of Although a direct effect on microtubules has not been demonstrated in these studies, morphologic evidence suggests that modification of enzyme secretion by colchicine and related agents occurs in parallel with depolymerization of macrophage microtubules (11,16). The efficacy of low doses of colchicine and inactivity of lumicolchicine are also consistent with such a relationship (9).…”

Studies on the Mechanism of Pathogenicity of Neisseria Gonorrhoeae

“…The constant concentration found during the whole period of infection may reflect an equilibrium between steady multiplication and death. If so, then colchicine-which interferes with the cellular regulation but has little effect on phagocytosis (Malawista and Bodel, 1967;Pesanti and Axline, 1975)-should be able to disrupt this chronic equilibrium. This prediction was confirmed.…”