THE MACROPHAGE ENDOTHELIAL-CELL MANNOSE RECEPTOR CDNA ENCODES A PROTEIN THAT BINDS OLIGOSACCHARIDES TERMINATING WITH SO4-4-GALNAC-BETA-1,4GLCNAC-BETA OR MAN AT INDEPENDENT SITES

Lutropin (LH) and other glycoproteins bearing oligosaccharides with th e terminal sequence SO4-4-GalNAc beta 1,4GlcNAc beta 1,4Man- (S4GGnM) are rapidly removed from the circulation by an S4GGnM-specific recepto r (S4GGnM-R) expressed at the surface of hepatic endothelial cells, Th e S4GGnM-R isolated from rat liver is closely related to the macrophag e mannose-specific receptor (Man-R) isolated from rat lung both antige nically and structurally, The S4GGnM-R and Man-R isolated from these t issues nonetheless differ in their ability to bind ligands bearing ter minal GalNAc-3-SO4 or Man. In this paper, we have explored the structu ral relationship between the Man-R and the S4GGnM-R by examining the p roperties of the recombinant Man-R in the form of a transmembrane prot ein and a soluble chimeric fusion protein in which the transmembrane a nd cytosolic domains have been replaced by the Fc region of human IgG1 . Like the S4GGnM-R isolated from liver, the chimeric fusion protein i s able to bind ligands terminating with GalNAc-4-SO4 and Man at indepe ndent sites. When expressed in CHO cells the recombinant Man-R is able to mediate the uptake of ligands bearing either terminal GalNAc-4-SO4 or terminal Man. We propose that the Man-R be renamed the Man/S4GGnM receptor on the basis of its multiple and independent specificities.