Commercially available complement component-depleted sera are unexpectedly codepleted of ficolin-2.

Commercially available complement component-depleted sera are unexpectedly codepleted of ficolin-2.
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市售的补体成分耗尽血清意外地同时去除了 ficolin-2。

DOI:
10.1128/cvi.00370-14
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发表时间:
2014
期刊:
Clinical and vaccine immunology : CVI
影响因子:
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通讯作者:
Nahm,MoonH
Nahm,MoonH
中科院分区:
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文献类型:
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作者:
Brady,AllisonM;Geno,KAaron;Dalecki,AlexG;Cheng,Xiaogang;Nahm,MoonH

文献摘要

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丝胶蛋白是一类先天模式识别分子,已知其可结合乙酰化化合物并通过甘露糖结合凝集素 (MBL)/丝胶蛋白相关丝氨酸蛋白酶 (MASP) 的结合激活补体。它们的重要性最近得到了重视,因为它们已被证明在从感染到自身免疫的各种疾病过程中发挥着作用。在研究 ficolin-2 介导的肺炎链球菌上的补体沉积时,我们发现去除 C1q 或其他补体成分的血清也同时去除了 ficolin-2,但没有去除 ficolin-1、ficolin-3 或 MBL。 C1q 耗尽血清中存在的 MBL 能够介导酿酒酵母上的补体沉积,表明 MASP 的存在。我们发现,仅在用外源重组 ficolin-2 (rFicolin-2) 调理后,C1q 耗尽血清中的肺炎球菌上的补体才会被激活。此外,当用赖氨酸 57 残基突变的 rFicolin-2 调理肺炎球菌时,在 C1q 耗尽的血清中没有观察到补体沉积,而已知 MASP 会与该残基结合。因此,这些耗尽的血清是研究 ficolin-2 介导的补体途径的独特工具。然而,人们应该意识到补体成分耗尽的血清中不存在 ficolin-2。
The ficolins are a family of innate pattern recognition molecules that are known to bind acetylated compounds and activate complement through the association of mannose binding lectin (MBL)/ficolin-associated serine proteases (MASPs). Their importance has more recently become appreciated, as they have been shown to play a role in a variety of disease processes from infection to autoimmunity. While studying ficolin-2-mediated complement deposition on Streptococcus pneumoniae, we found that sera depleted of C1q or other complement components were also codepleted of ficolin-2 but not ficolin-1, ficolin-3, or MBL. MBL present in C1q-depleted sera was able to mediate complement deposition on Saccharomyces cerevisiae, suggesting the presence of MASPs. We found that complement was activated on pneumococci in C1q-depleted serum only after opsonization with exogenous recombinant ficolin-2 (rFicolin-2). Also, no complement deposition was observed in C1q-depleted serum when pneumococci were opsonized with rFicolin-2 mutated at its lysine-57 residue, where MASPs are known to associate. Thus, these depleted sera are a unique tool to study ficolin-2-mediated complement pathways; however, one should be aware that ficolin-2 is absent from complement component-depleted sera.