Receptor-mediated endocytosis of fucosylated neoglycoprotein by macrophages.
The characteristics of the recognition system involved in the receptor mediated endocytosis of the neoglycoprotein, fucose-human serum albumin (HSA) were studied. It was found that (i) fucose-HSA showed strong affinity binding and uptake by various macrophages; (ii) binding was specific for L-fucose and D-mannose; (iii) binding was found to be inhibited by oxidant like H2O2 and swainsonine whereas it was elevated by dexamethasone; (iv) clearance of 125I-fucose-HSA was rapid and strongly inhibited by unlabelled fucose-HSA. Greater than 70% of fucose-HSA was found in liver and more than 60% of this was found in liver lysosomes; (v) uptake of fucose-HSA was thirty-fold more efficient in liver macrophages (Kupffer cells) than in hepatocytes; (vi) moreover, mannose-HSA and ovalbumin which are potent inhibitors of mannose/N-acetylglucosamine receptors inhibited clearance and uptake of fucose-HSA by liver as well as by isolated Kupffer cells suggesting the involvement of both fucose and mannose receptors or a single type of receptor having greater affinity for fucose-HSA than for mannose-HSA. These results emphasize the important role of fucose-terminated glycoproteins in site-specific drug targeting.
Sarkar
K
K
Department of Molecular Cell Biology, Indian Institute of Chemical Biology, Calcutta, India.
Sarkar
H S
HS
Kole
L
L
Das
P K
PK
D000818:Animals; D004705:Endocytosis; D006023:Glycoproteins / Q000378:metabolism* / Q000493:pharmacokinetics; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D014018:Tissue Distribution
D006023:Glycoproteins; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; C032193:glycoprotein receptor GPIb-IX