International Immunology, Vol. 15, No. 2, pp. 177-186,
February 2003
© 2003 Japanese Society for Immunology
FEATURED ARTICLE OF THE MONTH |
SIGN-R1, a novel C-type lectin expressed by marginal zone macrophages in spleen, mediates uptake of the polysaccharide dextran
1 Laboratory of Cellular Physiology and Immunology, and Chris Browne Center for Immunology and Immune Diseases, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA 2 Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan
Y.-S. K., S. Y. and T. I. are equally contributing first authors; R. M. S. and C. G. P. are equally contributing senior authors
Correspondence to: C. G. Park; E-mail. parkc{at}mail.rockefeller.edu
Transmitting editor: G. Trinchieri
The marginal zone macrophages of the spleen are implicated in the clearance of polysaccharides, but underlying mechanisms need to be pinpointed. SIGN-R1 is one of five recently identified mouse genes that are homologous to human DC-SIGN and encode a single, external, C-terminal C-type lectin domain. We find that a polyclonal antibody to a specific SIGN-R1 peptide reacts primarily and strongly with a subset of macrophages in the marginal zone of spleen and lymph node medulla. In both sites, SIGN-R1 exists primarily in an aggregated form, resistant to dissociation into monomers upon boiling in SDS under reducing conditions. Upon transfection into three different cell lines, high-mol.-wt forms bearing SIGN-R1 are expressed, as well as reactivity with ER-TR9, a mAb previously described to react selectively with marginal zone macrophages. SIGN-R1-expressing macrophages preferentially sequester dextrans following i.v. injection. Likewise, when phagocytic cells are enriched from spleen and tested in culture, dextran is selectively endocytosed by a subset of very large SIGN-R1+ cells representing 
5% of total released macrophages. Uptake of FITC–dextran by these macrophages in vivo and in vitro is blocked by ER-TR9 and polyclonal anti-SIGN-R1 antibodies. Following transfection with SIGN-R1, cell lines become competent to endocytose dextrans. The dextran localizes primarily to compartments lacking transferrin receptor and the LAMP-1 CD107a panlysosomal antigen. Therefore, SIGN-R1 mediates the uptake of dextran polysaccharides, and it is predominantly expressed in the macrophages of the splenic marginal zone and lymph node medulla.
Keywords: dextran, endocytosis, macrophage, marginal zone, SIGN-R1
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