Complement Receptor 1 Expression on Mouse Erythrocytes Mediates Clearance of Streptococcus pneumoniae by Immune Adherence
Complement Receptor 1 Expression on Mouse Erythrocytes Mediates Clearance of Streptococcus pneumoniae by Immune Adherence
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DOI：
10.1128/iai.01263-09
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发表时间：
2010-07-01
影响因子：
3.1
通讯作者：
Finberg, Robert W.
中科院分区：
文献类型：
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作者：
Li, Jie;Wang, Jennifer P.;Finberg, Robert W.
含有补体的免疫复合物可以通过携带补体受体1（CR1）的人红细胞呈递给吞噬细胞。虽然这一直被认为是人类能够保护自己免受“细胞外”细菌（如肺炎球菌）侵害的一种机制，但几乎没有直接证据。在这些研究中，我们通过比较红细胞上表达人CR1的转基因小鼠红细胞与不表达CR1的野生型小鼠红细胞的结果来研究这个问题。我们证明，在鼠红细胞上的人CR1表达允许免疫粘附到用小鼠或人血清作为补体来源调理的珠。CR1在免疫粘附中的作用得到了研究的支持，研究表明，向人CR1中加入抗体可以阻断CR1的作用。此外，人CR1表达在体外增强调理的肺炎球菌对红细胞的免疫粘附，并且通过CR1附着于红细胞的肺炎球菌可以在体外转移到活的巨噬细胞。更重要的是，我们观察到，如果将CR1（+）小鼠红细胞静脉注射到野生型小鼠体内（体外孵育短时间后），补体调理的肺炎球菌比类似地注射野生型小鼠红细胞的调理的肺炎球菌清除得更快。最后，我们已经表明，静脉内（i.v.）将肺炎双球菌注射到CR 1（+）小鼠中也会导致比野生型小鼠更快的血液清除。这些数据支持通过红细胞上的CR1的免疫粘附可能在从人血液中清除调理细菌中起重要作用。
Complement-containing immune complexes can be presented to phagocytes by human erythrocytes bearing complement receptor 1 (CR1). Although this has long been assumed to be a mechanism by which humans are able to protect themselves from "extracellular" bacteria such as pneumococci, there is little direct evidence. In these studies we have investigated this question by comparing results for erythrocytes from transgenic mice expressing human CR1 on their erythrocytes to the results for wild-type mouse erythrocytes that do not express CR1. We demonstrate that human CR1 expression on murine erythrocytes allows immune adherence to beads opsonized with either mouse or human serum as a source of complement. The role of CR1 in immune adherence was supported by studies showing that it was blocked by the addition of antibody to human CR1. Furthermore, human CR1 expression enhances the immune adherence of opsonized pneumococci to erythrocytes in vitro, and the pneumococci attached to erythrocytes via CR1 can be transferred in vitro to live macrophages. Even more importantly, we observed that if complement-opsonized pneumococci are injected intravenously with CR1(+) mouse erythrocytes into wild-type mice (after a short in vitro incubation), they are cleared faster than opsonized pneumococci similarly injected with wild-type mouse erythrocytes. Finally, we have shown that the intravenous (i.v.) injection of pneumococci into CR1(+) mice also results in more rapid blood clearance than in wild-type mice. These data support that immune adherence via CR1 on erythrocytes likely plays an important role in the clearance of opsonized bacteria from human blood.