Complement C3 and Activated Fragment C3a Are Involved in Complement Activation and Anti-Bacterial Immunity.

Complement C3 and Activated Fragment C3a Are Involved in Complement Activation and Anti-Bacterial Immunity.
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DOI:
10.3389/fimmu.2022.813173
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发表时间:
2022
影响因子:
7.3
通讯作者:
Li MF
Li MF
中科院分区:
医学2区
文献类型:
--
作者:
Wu M;Jia BB;Li MF

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在补体系统中,C3是补体激活、免疫防御和免疫调节的核心成分。在补体激活的所有途径中,关键步骤是将成分 C3 转化为 C3b 和 C3a,其负责消除病原体和调理作用。在这项研究中,我们检测了日本牙鲆 (Paralichthys olivaceus)(PoC3 和 PoC3a)的 C3 及其激活片段 C3a 的免疫学特性,日本牙鲆是一种具有重要经济价值的硬骨鱼。 PoC3由1655个氨基酸残基组成,包含C3家族的六个结构域和高度保守的GCGEQ序列。我们发现 PoC3 表达发生在九种不同的组织中,并且通过细菌攻击而上调。在血清中,PoC3能够与广谱细菌结合,纯化的天然PoC3可以直接杀死特定病原体。当日本牙鲆中的PoC3表达被siRNA敲除时,血清补体活性显着降低,并且鱼组织中的细菌复制显着增加。重组PoC3a(rPoC3a)对细菌和牙鲆外周血白细胞(PBL)表现出明显的结合能力,并诱导PBL的趋化性。给予 rPoC3a 的日本比目鱼表现出对细菌感染的抵抗力增强。综上所述,这些结果表明 PoC3 可能是补体激活的关键因素,并且 PoC3 和 PoC3a 是硬骨鱼抵抗细菌感染的最佳防御所必需的。
In the complement system, C3 is a central component in complement activation, immune defense and immune regulation. In all pathways of complement activation, the pivotal step is conversion of the component C3 to C3b and C3a, which is responsible to eliminate the pathogen and opsonization. In this study, we examined the immunological properties of C3 and its activated fragment C3a from Japanese flounder (Paralichthys olivaceus) (PoC3 and PoC3a), a teleost species with important economic value. PoC3 is composed of 1655 amino acid residues, contains the six domains and highly conserved GCGEQ sequence of the C3 family. We found that PoC3 expression occurred in nine different tissues and was upregulated by bacterial challenge. In serum, PoC3 was able to bind to a broad-spectrum of bacteria, and purified native PoC3 could directly kill specific pathogen. When PoC3 expression in Japanese flounder was knocked down by siRNA, serum complement activity was significantly decreased, and bacterial replication in fish tissues was significantly increased. Recombinant PoC3a (rPoC3a) exhibited apparent binding capacities to bacteria and Japanese flounder peripheral blood leukocytes (PBL) and induce chemotaxis of PBL. Japanese flounder administered rPoC3a exhibited enhanced resistance against bacterial infection. Taken together, these results indicate that PoC3 is likely a key factor of complement activation, and PoC3 and PoC3a are required for optimal defense against bacterial infection in teleost.
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影响因子: 8.2
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