Kang Young-Sun, Do Yoonkyung, Lee Hae-Kyung, Park Sung Ho, Cheong Cheolho, Lynch Rebecca M, Loeffler Jutta M, Steinman Ralph M, Park Chae Gyu
Laboratory of Cellular Physiology and Immunology and Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Cell. 2006 Apr 7;125(1):47-58. doi: 10.1016/j.cell.2006.01.046.
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. pneumoniae 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.
血清补体蛋白的复杂系统为抗感染提供了抵抗力。补体途径中的关键步骤是C3转化酶的组装，该酶消化C3补体成分以形成被白细胞识别的微生物结合C3片段。脾脏和C3对血源性肺炎链球菌感染具有抵抗力。为了更好地理解其中涉及的机制，我们研究了SIGN-R1，一种在脾脏中捕获微生物多糖的凝集素。令人惊讶的是，当静脉注射肺炎链球菌或其荚膜多糖时，条件性SIGN-R1基因敲除小鼠在C3分解代谢方面出现缺陷。血清C3的蛋白水解、C3在SIGN-R1(+)脾脏巨噬细胞内生物体上的沉积以及C3配体的形成均显著减少。我们发现SIGN-R1直接结合补体C1亚成分C1q，并组装了C3转化酶，但无需传统的抗体或B因子。因此，跨膜凝集素SIGN-R1通过一种不寻常的C3激活途径有助于先天抵抗力。
