The C-type lectin SIGN-R1 mediates uptake of the capsular polysaccharide of Streptococcus pneumoniae in the marginal zone of mouse spleen
The C-type lectin SIGN-R1 mediates uptake of the capsular polysaccharide of Streptococcus pneumoniae in the marginal zone of mouse spleen
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DOI：
10.1073/pnas.0307124101
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发表时间：
2004-01-06
影响因子：
11.1
通讯作者：
Park, CG
中科院分区：
文献类型：
--
作者：
Kang, YS;Kim, JY;Park, CG
SIGN-R1是最近发现的C型凝集素，在脾边缘区的巨噬细胞上高水平表达，介导这些吞噬细胞对葡聚糖多糖的摄取。我们现在发现，被包裹的肺炎链球菌被这些巨噬细胞从血流中迅速清除，并且当不同的细胞系在转染后表达SIGN-R1时也会发生捕获。目的：探讨S.在SIGN-R1与肺炎球菌相互作用中，我们首先研究了血清型14 CPS在转染细胞中的结合和摄取。观察到结合，并且对CPS 14的亲合力比葡聚糖高得多（3，000倍）。来自四种不同血清型的CPS在体内也被边缘区巨噬细胞清除。为了确定SIGN-R1在这种摄取中的作用，我们通过用SIGN-R1抗体预处理小鼠来选择性地下调凝集素的表达，包括新产生的仓鼠单克隆抗体22 D1。在这种瞬时敲除后的几天内，边缘区巨噬细胞无法摄取CPS或葡聚糖。因此，小鼠边缘区巨噬细胞具有与荚膜肺炎球菌多糖相互作用的受体，为进一步研究这种相互作用的功能后果奠定了基础。
SIGN-R1, a recently discovered C-type lectin expressed at high levels on macrophages within the marginal zone of the spleen, mediates the uptake of dextran polysaccharides by these phagocytes. We now find that encapsulated Streptococcus pneumoniae are rapidly cleared by these macrophages from the bloodstream, and that capture also takes place when different cell lines express SIGN-R1 after transfection. To assess the role of the capsular polysaccharide of S. pneumoniae (CPS) in the interaction of SIGN-R1 with pneumococci, we first studied binding and uptake of serotype 14 CPS in transfected cells. Binding was observed and was of a much higher avidity (3,000-fold) for CPS 14 than dextran. The CPSs from four different serotypes were also cleared by marginal zone macrophages in vivo. To establish a role for SIGN-R1 in this uptake, we selectively down-regulated expression of the lectin by pretreatment of the mice with SIGN-R1 antibodies, including a newly generated hamster monoclonal called 22D1. For several days after this transient knockout, the marginal zone macrophages were unable to take up either CPSs or dextrans. Therefore, marginal zone macrophages in mice have a receptor that interacts with capsular pneumococcal polysaccharides, setting the stage for further studies of the functional consequences of this interaction.