title: SIGN-R1, a novel C-type lectin expressed by marginal zone macrophages in spleen, mediates uptake of the polysaccharide dextran.
abstract: 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 approximately 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.
authors.affiliation: 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.
authors.forename: Young-Sun
authors.initials: YS
authors.lastname: Kang
authors.forename: Sayuri
authors.initials: S
authors.lastname: Yamazaki
authors.forename: Tomonori
authors.initials: T
authors.lastname: Iyoda
authors.forename: Maggie
authors.initials: M
authors.lastname: Pack
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Bruening
authors.forename: Jae Y
authors.initials: JY
authors.lastname: Kim
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Takahara
authors.forename: Kayo
authors.initials: K
authors.lastname: Inaba
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Steinman
authors.forename: Chae Gyu
authors.initials: CG
authors.lastname: Park
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics; D003911:Dextrans / Q000378:metabolism*; D007150:Immunohistochemistry; D037181:Lectins, C-Type / Q000235:genetics* / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011956:Receptors, Cell Surface / Q000235:genetics; D013154:Spleen / Q000378:metabolism*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D003911:Dextrans; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin