Role of Fc in antibody-mediated protection from ricin toxin.

Role of Fc in antibody-mediated protection from ricin toxin.
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DOI:
10.3390/toxins6051512
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发表时间:
2014-05-07
期刊:
影响因子:
4.2
通讯作者:
Berry J
Berry J
中科院分区:
医学2区
文献类型:
--
作者:
Pincus SH;Das A;Song K;Maresh GA;Corti M;Berry J

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我们研究了抗体(Ab)Fc区在介导蓖麻毒素毒性保护中的作用。我们比较了来自两种不同的中和抗体制剂的完整Ig和Fab片段的体外和体内效果,其中一种是单克隆的,另一种是多克隆的。结果一致,Ig和Fab在抗原结合和体外中和方面差异不大,但在保护动物方面有较大差异。我们还研究了通过Fc受体向细胞内导入抗体是否增强了胞内蓖麻毒素的中和作用。我们发现,进口的抗体存在于胞浆内质网和高尔基体中,后者是蓖麻毒素穿过细胞的一个隔室,但胞内抗体对蓖麻毒素的中和作用没有贡献。这些结果表明,抗体的Fc区对于体内保护是重要的,尽管完整免疫球蛋白增强保护的机制似乎不是在单细胞水平上起作用的。当使用异种抗体时,Fab/F(ab‘)2制剂的免疫原性减弱应与可能丧失的保护效力相平衡。
We have studied the role of the antibody (Ab) Fc region in mediating protection from ricin toxicity. We compared the in vitro and in vivo effects of intact Ig and of Fab fragments derived from two different neutralizing Ab preparations, one monoclonal, the other polyclonal. Consistent results were obtained from each, showing little difference between Ig and Fab in terms of antigen binding and in vitro neutralization, but with relatively large differences in protection of animals. We also studied whether importing Ab into the cell by Fc receptors enhanced the intracellular neutralization of ricin toxin. We found that the imported Ab was found in the ER and Golgi, a compartment traversed by ricin, as it traffics through the cell, but intracellular Ab did not contribute to the neutralization of ricin. These results indicate that the Fc region of antibody is important for in vivo protection, although the mechanism of enhanced protection by intact Ig does not appear to operate at the single cell level. When using xenogeneic antibodies, the diminished immunogenicity of Fab/F(ab’)2 preparations should be balanced against possible loss of protective efficacy.
DOI: 10.3390/toxins4060430
发表时间: 2012-06
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影响因子: 4.2
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影响因子: 3.7
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