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 album in (HSA) were studied. It was found that (i) fucose-HSA showed strong affinity binding and uptake by various macrophages; (ii) binding was s pecific for L-fucose and D-mannose; (iii) binding was found to be inhi bited by oxidant like H2O2 and swainsonine whereas it was elevated by dexamethasone; (iv) clearance of I-125-fucose-HSA was rapid and strong ly 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 lysoso mes; (v) uptake of fucose-HSA was thirty-fold more efficient in liver macrophages (Kupffer cells) than in hepatocytes; (vi) moreover, mannos e-HSA and ovalbumin which are potent inhibitors of mannose/N-acetylglu cosamine receptors inhibited clearance and uptake of fucose-HSA by liv er 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 em phasize the important role of fucose-terminated glycoproteins in site- specific drug targeting.