A dominant complement fixation pathway for pneumococcal polysaccharides initiated by SIGN-R1 interacting with C1q
A dominant complement fixation pathway for pneumococcal polysaccharides initiated by SIGN-R1 interacting with C1q
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DOI：
10.1016/j.cell.2006.01.046
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发表时间：
2006-04-07
期刊：
影响因子：
64.5
通讯作者：
Park, CG
中科院分区：
文献类型：
--
作者：
Kang, YS;Do, YY;Park, CG
复杂的血清补体蛋白系统提供对感染的抵抗力。补体途径中的关键步骤是C3转化酶的组装，其使C3补体组分降解以形成由白细胞识别的微生物结合C3片段。脾脏和C3提供对血源性S的抵抗力。肺炎感染为了更好地理解所涉及的机制，我们研究了SIGN-R1，一种捕获脾脏中微生物多糖的凝集素。令人惊讶的是，条件性SIGN-R1敲除小鼠在给予S.肺炎克雷伯菌或其荚膜多糖静脉注射。血清C3的蛋白水解、SIGN-R1（+）脾巨噬细胞内生物体上C3的沉积和C3配体的形成显著减少。我们发现SIGN-R1直接结合补体C1亚组分C1 q，并组装C3转化酶，但不需要传统的抗体或因子B。因此，跨膜凝集素SIGN-R1通过一种不寻常的C3激活途径促进先天抗性。
The intricate system of serum complement proteins provides resistance to infection. A pivotal step in the complement pathway is the assembly of a C3 convertase, which digests the C3 complement component to form microbial binding C3 fragments recognized by leukocytes. The spleen and C3 provide resistance against blood-borne S. pneurnomae infection. To better understand the mechanisms involved, we studied SIGN-R1, a lectin that captures microbial polysaccharides in spleen. Surprisingly, conditional SIGN-R1 knockout mice developed deficits in C3 catabolism when given S. pneumoniae or its capsular polysaccharide intravenously. There were marked reductions in proteolysis of serum C3, deposition of C3 on organisms within SIGN-R1(+) spleen macrophages, and formation of C3 ligands. We found that SIGN-R1 directly bound the complement C1 subcomponent, C1q, and assembled a C3 convertase, but without the traditional requirement for either antibody or factor B. The transmembrane lectin SIGN-R1 therefore contributes to innate resistance by an unusual C3 activation pathway.