Mannose-receptor ligands stimulate secretion of lysosomal enzymes from rabbit alveolar macrophages.
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.
D000118:Acetylglucosaminidase / Q000378:metabolism*; D000818:Animals; D006023:Glycoproteins / Q000138:chemical synthesis / Q000494:pharmacology*; D006596:Hexosaminidases / Q000378:metabolism*; D007700:Kinetics; D037181:Lectins, C-Type; D008024:Ligands; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology*; D008358:Mannose / Q000378:metabolism; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011107:Polylysine / Q000494:pharmacology; D011817:Rabbits; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000187:drug effects / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000494:pharmacology
D006023:Glycoproteins; D037181:Lectins, C-Type; D008024:Ligands; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D011107:Polylysine; D012710:Serum Albumin, Bovine; D006596:Hexosaminidases; D000118:Acetylglucosaminidase; D008358:Mannose