Microbe-specific C3b deposition in the horseshoe crab complement system in a C2/factor B-dependent or -independent manner.

Microbe-specific C3b deposition in the horseshoe crab complement system in a C2/factor B-dependent or -independent manner.
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DOI:
10.1371/journal.pone.0036783
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Kawabata S
Kawabata S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Tagawa K;Yoshihara T;Shibata T;Kitazaki K;Endo Y;Fujita T;Koshiba T;Kawabata S

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补体C3在哺乳动物补体系统中对病原体的调理起着至关重要的作用,而在无脊椎动物中C3激活的分子机制尚不清楚。为了了解C3b在微生物上沉积的分子机制,我们对从鲎(Tachypleus tridentatus)中鉴定的两种C2/因子B同源物TtC2/Bf-1和TtC2/Bf-2进行了研究。虽然TtC2/Bf-1和TtC2/Bf-2的结构域结构与哺乳动物同源物相同,但它们在n端分别含有5重复和7重复的补体控制蛋白结构域。TtC2/Bf-1和TtC2/Bf-2在血细胞中合成并糖基化,分泌到血淋巴血浆中,与C3形成复合物(TtC3),其被微生物激活完全依赖于Mg2+。流式细胞分析显示TtC3b沉积对革兰氏阳性菌或真菌具有Mg2+依赖性,而对革兰氏阴性菌不具有Mg2+依赖性。此外,该分析表明,TtC3b在革兰氏阳性细菌上沉积需要Ca2+依赖性凝集素(c -反应蛋白-1和tachylectin-5A),而TtC3b在真菌上沉积绝对需要Ca2+非依赖性凝集素(Tachypleus血浆凝集素-1)。相反,马蹄蟹脂多糖敏感蛋白酶因子C是将TtC3b沉积在革兰氏阴性菌上的必要和充分条件。我们得出结论,血浆凝集素和因子C以C2/因子b依赖或不依赖的方式在微生物特异性TtC3b沉积中发挥关键作用。
Complement C3 plays an essential role in the opsonization of pathogens in the mammalian complement system, whereas the molecular mechanism underlying C3 activation in invertebrates remains unknown. To understand the molecular mechanism of C3b deposition on microbes, we characterized two types of C2/factor B homologs (designated TtC2/Bf-1 and TtC2/Bf-2) identified from the horseshoe crab Tachypleus tridentatus. Although the domain architectures of TtC2/Bf-1 and TtC2/Bf-2 were identical to those of mammalian homologs, they contained five-repeated and seven-repeated complement control protein domains at their N-terminal regions, respectively. TtC2/Bf-1 and TtC2/Bf-2 were synthesized and glycosylated in hemocytes and secreted to hemolymph plasma, which existed in a complex with C3 (TtC3), and their activation by microbes was absolutely Mg2+-dependent. Flow cytometric analysis revealed that TtC3b deposition was Mg2+-dependent on Gram-positive bacteria or fungi, but not on Gram-negative bacteria. Moreover, this analysis demonstrated that Ca2+-dependent lectins (C-reactive protein-1 and tachylectin-5A) were required for TtC3b deposition on Gram-positive bacteria, and that a Ca2+-independent lectin (Tachypleus plasma lectin-1) was definitely indispensable for TtC3b deposition on fungi. In contrast, a horseshoe crab lipopolysaccharide-sensitive protease factor C was necessary and sufficient to deposit TtC3b on Gram-negative bacteria. We conclude that plasma lectins and factor C play key roles in microbe-specific TtC3b deposition in a C2/factor B-dependent or -independent manner.
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影响因子: 4.8
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影响因子: 4.4
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发表时间: 1999-08-31
影响因子: 11.1
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通讯作者: Kawabata, S