LIGAND SIZE IS A MAJOR DETERMINANT OF HIGH-AFFINITY BINDING OF FUCOSE-EXPOSING AND GALACTOSE-EXPOSING (LIPO)PROTEINS BY THE HEPATIC FUCOSE RECEPTOR

Previous in vivo studies have demonstrated that small galactose-exposi ng particles are preferentially internalized by the asialoglycoprotein receptor on the parenchymal liver cell and large particles by the gal actose-particle receptor on the Kupffer cell. In this study, we have i nvestigated using in vitro binding studies whether the affinity for ei ther receptor is affected by the ligand size. The asialoglycoprotein r eceptor appeared to bind and process lactosylated proteins irrespectiv e of their size. In contrast, recognition of galactose-exposing protei ns by the galactose-particle receptor on the Kupffer cell was strongly dependent on size. The affinity increased 3000-fold with protein size s increasing from 5 to 15 nm, reaching its maximum at approx. 1 nM for ligands larger than 15 nm. Apparently, the preferential in vivo uptak e of large galactose-exposing ligands by Kupffer cells does not result from an inability of the parenchymal liver cells to internalize these ligands, but from the high affinity of large ligands for the galactos e-particle receptor and the strategic anatomical localization of the K upffer cells in the liver. In the preceding paper [Kuiper, Bakkeren, B iessen and Van Berkel (1994) Biochem. J. 299, 285-290] the galactose-p article receptor on the Kupffer cell was suggested to be identical wit h the fucose receptor. I-125-Lac-LDL-binding studies clearly showed th at the galactose-particle receptor exhibited high-affinity binding of fucose-exposing proteins also. The affinity of fucosylated proteins fo r the galactose-particle receptor was greatly affected by ligand size. The above data strongly support the hypothesis that the galactose-par ticle receptor is identical with the fucose receptor. The size of neog lycoproteins can be appreciated as a new major determinant of affinity for the fucose receptor.