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  • Title: Mannose-receptor ligands stimulate secretion of lysosomal enzymes from rabbit alveolar macrophages.
    Author: Ohsumi Y, Lee YC.
    Journal: J Biol Chem; 1987 Jun 15; 262(17):7955-62. PubMed ID: 3597356.
    Abstract:
    Neoglycoproteins (Lee, Y.C., Stowell, C.P., and Krantz, M.J. (1976) Biochemistry 15, 3956-3963) and monosaccharides which interact with the Man/Fuc receptor (Stah, P.D., Rodman, J.S., Miller, M.J., and Schlesinger, P.H. (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 1399-1403) stimulate lysosomal enzyme secretion in rabbit alveolar macrophages in a dose- and time-dependent fashion. Man43-bovine serum albumin (BSA), L-Fuc30-BSA, and Man96-poly-D-lysine (Hoppe, C.A., and Lee, Y.C. (1984) Biochemistry 23, 1723-1730) were potent stimulators of lysosomal enzyme secretion. Mannose, L-fucose (Fuc), N-acetylmannosamine and N-acetylglucosamine were also effective, but much higher concentrations (above 10 mM) were required to elicit the same effects as the corresponding neoglycoproteins. After a 1.5-h incubation of the cells with Man43-BSA in the presence of 10 mM EDTA, the stimulation of lysosomal enzyme secretion was reduced by 73%. These results indicate that the Man/L-Fuc receptor participates in the process of lysosomal enzyme secretion. Addition of cycloheximide did not affect the stimulation by Man43-BSA, indicating that shunting of newly synthesized enzymes is not involved in the observed phenomenon. The temporary binding of ligands to the cell surface Man/Fuc receptor at 4 degrees C also did not show the stimulation effect. Secretion of Man211-poly-D-lysine preloaded in secondary lysosome was stimulated by Man43-BSA, suggesting that secondary lysosome is one of the pools from which lysosomal enzymes are secreted. However, neither storage of an undegradable ligand in lysosomes nor the degradation of a degradable ligand was an absolute requirement for stimulation of enzyme secretion, because both Man96-poly-D-lysine (nondegradable ligand) and Man43-BSA (degradable ligand) can stimulate to a similar extent.
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