Complement activation by PEGylated single-walled carbon nanotubes is independent of C1q and alternative pathway turnover.
Complement activation by PEGylated single-walled carbon nanotubes is independent of C1q and alternative pathway turnover.
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DOI：
10.1016/j.molimm.2008.05.020
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发表时间：
2008-08
影响因子：
3.6
通讯作者：
Moein Moghimi S
中科院分区：
文献类型：
--
作者：
Hamad I;Christy Hunter A;Rutt KJ;Liu Z;Dai H;Moein Moghimi S
我们研究了长循环聚乙二醇稳定的单壁碳纳米管（SWNTs）和补体系统之间的相互作用。氨基聚（乙二醇）5000-二硬脂酰磷脂酰乙醇胺（Aminopoly（ethylene glycol）5000-DSPE）和甲氧基PEG 5000-DSPE包被的生长态HIPco单壁碳纳米管在未稀释的正常人血清中激活补体，这反映在C4 d和SC 5 b-9水平的显著升高，但不是旁路途径分裂产物Bb，因此表明仅通过C4裂解激活。在C2耗尽血清中的研究证实，PEG化纳米管介导的SC 5 b-9升高是C4 b2 a转化酶依赖性的。借助于针对C1 s的单克隆抗体和去除C1 q的人血清，也显示出在去除C1 q的血清中纳米管介导的补体活化不依赖于经典途径。然而，在C1 q耗尽的血清中，纳米管介导的C4d升高被N-乙酰葡糖胺、Futhan（一种能够通过所有三种途径阻止补体活化的广谱丝氨酸蛋白酶抑制剂）和抗MASP-2抗体抑制;这强烈表明MASP-2的活化在随后的C4切割和C4 b2 a转化酶组装中的作用。在一些大鼠中静脉注射PEG化纳米管与血浆血栓素B2水平的显著升高相关，表明体内纳米管介导的补体激活。这些观察结果的临床意义进行了讨论。
We have investigated the interaction between long circulating poly(ethylene glycol)-stabilized single-walled carbon nanotubes (SWNTs) and the complement system. Aminopoly(ethylene glycol)5000–distearoylphosphatidylethanolamine (aminoPEG5000–DSPE) and methoxyPEG5000–DSPE coated as-grown HIPco SWNTs activated complement in undiluted normal human serum as reflected in significant rises in C4d and SC5b-9 levels, but not the alternative pathway split-product Bb, thus indicating activation exclusively through C4 cleavage. Studies in C2-depleted serum confirmed that PEGylated nanotube-mediated elevation of SC5b-9 was C4b2a convertase-dependent. With the aid of monoclonal antibodies against C1s and human serum depleted from C1q, nanotube-mediated complement activation in C1q-depleted serum was also shown to be independent of classical pathway. Nanotube-mediated C4d elevation in C1q-depleted serum, however, was inhibited by N-acetylglucosamine, Futhan (a broad-spectrum serine protease inhibitor capable of preventing complement activation through all three pathways) and anti-MASP-2 antibodies; this strongly suggests a role for activation of MASP-2 in subsequent C4 cleavage and assembly of C4b2a covertases. Intravenous injection of PEGylated nanotubes in some rats was associated with a significant rise in plasma thromboxane B2 levels, indicative of in vivo nanotube-mediated complement activation. The clinical implications of these observations are discussed.
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影响因子：
3.4
作者：
Dos Santos, Nancy;Allen, Christine;Bally, Marcel B.
通讯作者：
Bally, Marcel B.
DOI：
10.1073/pnas.0707654105
发表时间：
2008-02-05
影响因子：
11.1
作者：
Liu, Zhuang;Davis, Corrine;Dai, Hongjie
通讯作者：
Dai, Hongjie
影响因子：
4.4
作者：
Matsushita, M;Endo, Y;Fujita, T
通讯作者：
Fujita, T
影响因子：
4.4
作者：
Andersson, J;Ekdahl, KN;Nilsson, B
通讯作者：
Nilsson, B
影响因子：
3.5
作者：
Gbadamosi, JK;Hunter, AC;Moghimi, SM
通讯作者：
Moghimi, SM