Immature Human Dendritic Cells Express Asialoglycoprotein Receptor Isoforms for Efficient Receptor-Mediated Endocytosis

• Published in: The Journal of immunology (1950) 2001-11, Vol.167 (10), p.5767-5774
• Main Authors: Valladeau, Jenny, Duvert-Frances, Valerie, Pin, Jean-Jacques, Kleijmeer, Monique J, Ait-Yahia, Smina, Ravel, Odile, Vincent, Claude, Vega, Felix, Jr, Helms, Alison, Gorman, Dan, Zurawski, Sandra M, Zurawski, Gerard, Ford, John, Saeland, Sem
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Asialoglycoprotein Receptor; Asialoglycoprotein receptors; CD40 Antigens - metabolism; Cells, Cultured; Cloning, Molecular; DC-ASGPR protein; Dendritic Cells - immunology; Endocytosis; Endosomes - chemistry; Granulocytes - immunology; Humans; Lectins - genetics; Lectins, C-Type; Membrane Proteins - genetics; Mice; Molecular Sequence Data; Monocytes - immunology; Phylogeny; Rats; Receptors, Cell Surface - biosynthesis; Receptors, Cell Surface - genetics; Receptors, Cell Surface - physiology; RNA, Messenger - biosynthesis; Sequence Homology, Amino Acid; Stem Cells - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.167.10.5767

In a search for genes expressed by dendritic cells (DC), we have cloned cDNAs encoding different forms of an asialoglycoprotein receptor (ASGPR). The DC-ASGPR represents long and short isoforms of human macrophage lectin, a Ca(2+)-dependent type II transmembrane lectin displaying considerable homology with the H1 and H2 subunits of the hepatic ASGPR. Immunoprecipitation from DC using an anti-DC-ASGPR mAb yielded a major 40-kDa protein with an isoelectric point of 8.2. DC-ASGPR mRNA was observed predominantly in immune tissues. Both isoforms were detected in DC and granulocytes, but not in T, B, or NK cells, or monocytes. DC-ASGPR species were restricted to the CD14-derived DC obtained from CD34(+) progenitors, while absent from the CD1a-derived subset. Accordingly, both monocyte-derived DC and tonsillar interstitial-type DC expressed DC-ASGPR protein, while Langerhans-type cells did not. Furthermore, DC-ASGPR is a feature of immaturity, as expression was lost upon CD40 activation. In agreement with the presence of tyrosine-based and dileucine motifs in the intracytoplasmic domain, mAb against DC-ASGPR was rapidly internalized by DC at 37 degrees C. Finally, intracellular DC-ASGPR was localized to early endosomes, suggesting that the receptor recycles to the cell surface following internalization of ligand. Our findings identify DC-ASGPR/human macrophage lectin as a feature of immature DC, and as another lectin important for the specialized Ag-capture function of DC.