Collectin-11/MASP Complex Formation Triggers Activation of the Lectin Complement Pathway - The Fifth Lectin Pathway Initiation Complex
Collectin-11/MASP Complex Formation Triggers Activation of the Lectin Complement Pathway - The Fifth Lectin Pathway Initiation Complex
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DOI：
10.1159/000345356
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发表时间：
2013-01-01
影响因子：
5.3
通讯作者：
Garred, Peter
中科院分区：
文献类型：
--
作者：
Ma, Ying Jie;Skjoedt, Mikkel-Ole;Garred, Peter
收集物和纤维蛋白在清除内源性和外源性危险物质中起重要作用。最近在血清中发现了一种新的低浓度的人收集素-11，它与甘露糖结合凝集素(MBL)/菲可林相关丝氨酸蛋白酶复合物存在。收集素-11与存在于各种微生物上的碳水化合物残基结合。因此，我们推测收集素-11可能是补体凝集素途径中一个新的起始分子。我们可以证明，集合素-11与所有已知的mbl相关丝氨酸蛋白酶（MASP-1、MASP-2和MASP-3）以及凝集素补体途径调节因子MAP-1相关。此外，我们发现重组collectin-11和重组MASP-2在白色念珠菌上形成复合物导致C4b沉积。血清中天然收集素-11介导C4b和C3b的补体激活和沉积，以及白色念珠菌末端补体复合物的形成。此外，用重组集合素-11刺激缺乏集合素-11的血清（不介导补体激活）可以恢复补体激活能力。这些结果将collectin-11定义为除了MBL、ficolin-1、ficolin-2和ficolin-3之外，在凝集素补体途径中的第五个识别分子。巴塞尔S. Karger股份有限公司版权所有
Collectins and ficolins are important in the clearance of endogenous and exogenous danger materials. A new human collectin-11 was recently identified in low concentration in serum in complex with mannose-binding lectin (MBL)/ficolin-associated serine proteases. Collectin-11 binds to carbohydrate residues present on various microorganisms. Thus, we hypothesized that collectin-11 could be a novel initiation molecule in the lectin pathway of complement. We can show that collectin-11 associates with all the known MBL-associated serine proteases (MASP-1, MASP-2 and MASP-3) as well as the lectin complement pathway regulator MAP-1. Furthermore, we found that complex formation between recombinant collectin-11 and recombinant MASP-2 on Candida albicans leads to deposition of C4b. Native collectin-11 in serum mediated complement activation and deposition of C4b and C3b, and formation of the terminal complement complex on C. albicans. Moreover, spiking collectin-11-depleted serum, which did not mediate complement activation, with recombinant collectin-11 restored the complement activation capability. These results define collectin-11 as the fifth recognition molecule in the lectin complement pathway in addition to MBL, ficolin-1, ficolin-2 and ficolin-3. Copyright (C) 2012 S. Karger AG, Basel