SIGN-R1, a novel C-type lectin expressed by marginal zone macrophages in spleen, mediates uptake of the polysaccharide dextran

被引:136
作者
Kang, YS
Yamazaki, S
Iyoda, T
Pack, M
Bruening, SA
Kim, JY
Takahara, K
Inaba, K
Steinman, RM
Park, CG
机构
[1] Rockefeller Univ, Cellular Physiol & Immunol Lab, New York, NY 10021 USA
[2] Rockefeller Univ, Chris Browne Ctr Immunol & Immune Dis, New York, NY 10021 USA
[3] Kyoto Univ, Dept Anim Dev & Physiol, Grad Sch Biostudies, Kyoto 6068502, Japan
关键词
dextran; endocytosis; macrophage; marginal zone; SIGN-R1;
D O I
10.1093/intimm/dxg019
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 similar to5% 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-RI, 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.
引用
收藏
页码:177 / 186
页数:10
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