FcRn-mediated intestinal absorption of IgG anti-IgE/IgE immune complexes in mice.
FcRn-mediated intestinal absorption of IgG anti-IgE/IgE immune complexes in mice.
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DOI：
10.1111/j.1365-2222.2012.04043.x
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发表时间：
2012-12
期刊：
影响因子：
--
通讯作者：
Matson AP
中科院分区：
文献类型：
--
作者：
Paveglio S;Puddington L;Rafti E;Matson AP
负责获得IgG以外的母体抗体同种型的机制尚未完全了解。确定新生儿IgG摄取Fc受体（FcRn）介导IgG 1抗IgE/IgE免疫复合物肠道吸收的能力。产生C57 BL/6过敏性卵清蛋白（OVA）免疫的寄养母亲以养育幼稚FcRn+/−或FcRn−/−后代。在断奶时，测定过敏性养母和FcRn+/+、FcRn+/−或FcRn −/−母乳喂养后代的血清OVA特异性抗体和IgG 1抗IgE/IgE免疫复合物水平。在单独的实验中，对FcRn+/−或FcRn−/−新生小鼠灌胃喂食TNP特异性IgE（作为IgG 1抗IgE/IgE免疫复合物）、IgG 1同种型对照和IgE或单独的IgE。喂食后2小时处死小鼠，以测定吸收的TNP特异性IgE的血清水平和生物活性。正如预期，FcRn−/−后代中母体OVA特异性IgG 1的吸收水平比FcRn+/+或FcRn+/−后代中观察到的低103-104。令人惊讶的是，FcRn表达也影响母体IgE的吸收。在FcRn+/+和FcRn+/−后代中检测到OVA特异性IgE，但在FcRn−/−后代中未检测到。在过敏性养母中检测到IgG 1抗IgE/IgE免疫复合物，并与FcRn+/+和FcRn+/−后代的水平密切相关（rho=0.88，P <0.0001）。此外，FcRn表达是新生小鼠在以IgG 1抗IgE/IgE免疫复合物喂养时吸收TNP特异性IgE所必需的。当用针对Cε4结构域的IgG 1抗IgE产生免疫复合物时，吸收的IgE能够在抗原依赖性嗜碱性粒细胞脱粒中起作用。这些数据证明了一种新的机制，通过该机制，FcRn可以促进IgG以外的母体抗体的吸收。这些发现具有临床相关性，因为FcRn介导母体IgG经胎盘进入胎儿。这提出了FcRn可能介导母体IgE作为IgG抗IgE/IgE免疫复合物经胎盘通过的可能性。
The mechanism(s) responsible for the acquisition of maternal antibody isotypes other than IgG are not fully understood. To define the ability of the neonatal Fc receptor for IgG uptake (FcRn) to mediate intestinal absorption of IgG1 anti-IgE/IgE immune complexes. C57BL/6 allergic ovalbumin (OVA)-immune foster mothers were generated to nurse naïve FcRn+/− or FcRn−/− progeny. At the time of weaning, serum levels of OVA-specific antibodies and IgG1 anti-IgE/IgE immune complexes were determined in allergic foster mothers and FcRn+/+, FcRn+/−, or FcRn−/− breastfed offspring. In separate experiments, FcRn+/− or FcRn−/− neonatal mice were gavage fed TNP-specific IgE as IgG1 anti-IgE/IgE immune complexes, IgG1 isotype control and IgE, or IgE alone. Mice were sacrificed 2 hours after feeding to determine serum levels and biologic activity of absorbed TNP-specific IgE. As expected, the absorption of maternal OVA-specific IgG1 in FcRn−/− offspring was at levels 103–104 less than observed in FcRn+/+ or FcRn+/− offspring. Surprisingly, FcRn expression also influenced the absorption of maternal IgE. OVA-specific IgE was detected in FcRn+/+ and FcRn+/− offspring, but not in FcRn−/− offspring. IgG1 anti-IgE/IgE immune complexes were detected in allergic foster mothers and correlated strongly with levels in FcRn+/+ and FcRn+/− offspring (rho=0.88, P <0.0001). Furthermore, FcRn expression was required for neonatal mice to absorb TNP-specific IgE when fed as IgG1 anti-IgE/IgE immune complexes. When immune complexes were generated with IgG1 anti-IgE directed against the Cε4 domain, the absorbed IgE was able to function in antigen-dependent basophil degranulation. These data demonstrate a novel mechanism by which FcRn may facilitate absorption of maternal antibodies other than IgG. These findings are clinically relevant because FcRn mediates the transplacental passage of maternal IgG to the fetus. This raises the possibility that FcRn could mediate the transplacental passage of maternal IgE as IgG anti-IgE/IgE immune complexes.
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影响因子：
4.4
作者：
Matson, Adam P.;Zhu, Li;Puddington, Lynn
通讯作者：
Puddington, Lynn
影响因子：
15.9
作者：
BUSE, MG;BUSE, J;ROBERTS, WJ
通讯作者：
ROBERTS, WJ
影响因子：
6
作者：
Maidji, E;McDonagh, S;Pereira, L
通讯作者：
Pereira, L
影响因子：
2.8
作者：
Bieber, Thomas
通讯作者：
Bieber, Thomas
DOI：
10.1089/bfm.2008.0130
发表时间：
2009-09
期刊：
Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine
影响因子：
--
作者：
Matson AP;Thrall RS;Rafti E;Puddington L
通讯作者：
Puddington L