Targeted delivery of superoxide dismutase to macrophages via mannose receptor-mediated mechanism.
Human recombinant superoxide dismutase (SOD) was modified into a mannosylated form (Man-SOD), and its cellular uptake and inhibitory effect on superoxide anion release were studied in vitro, using cultured mouse peritoneal macrophages. [111In]Man-SOD was taken up by the macrophages to a great extent, whereas no significant uptake was observed for native and galactosylated SOD. The uptake of Man-SOD was inhibited significantly at a low temperature and by the presence of mannan, mannose and colchicine, demonstrating the targeted delivery of Man-SOD via mannose receptor-mediated endocytosis. Man-SOD exhibited a superior inhibitory effect on superoxide anion release from inflammatory macrophages stimulated by phorbol-myristate acetate. The present study suggested the potential of Man-SOD as a therapeutic agent for the inflammatory disease mediated by superoxide anions generated by macrophages.
Takakura
Y
Y
Department of Basic Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Masuda
S
S
Tokuda
H
H
Nishikawa
M
M
Hashida
M
M
D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D037181:Lectins, C-Type; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D051379:Mice; D008813:Mice, Inbred ICR; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D013481:Superoxides / Q000037:antagonists & inhibitors
D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D013481:Superoxides; D013482:Superoxide Dismutase