Intravenous neuromyelitis optica autoantibody in mice targets aquaporin-4 in peripheral organs and area postrema.
Intravenous neuromyelitis optica autoantibody in mice targets aquaporin-4 in peripheral organs and area postrema.
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DOI：
10.1371/journal.pone.0027412
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Verkman AS
中科院分区：
文献类型：
--
作者：
Ratelade J;Bennett JL;Verkman AS
视神经肌萎缩症（NMO）的发病机制涉及IgG自身抗体（NMO-IgG）与中枢神经系统（CNS）星形胶质细胞上的水通道蛋白4（AQP 4）的结合。我们研究了在小鼠体内处理的重组单克隆人NMO-IgG，强烈结合小鼠AQP 4。静脉给药后，血清[NMO-IgG]在野生型小鼠中随着t1/2降低至18小时，在AQP 4敲除小鼠中随着t1/2降低至41小时。NMO-IgG定位于肾脏（集合管）、骨骼肌、气管（上皮细胞）和胃（壁细胞）中表达AQP 4的细胞膜。NMO-IgG在脑最后区的星形胶质细胞上可见，而在脑、脊髓、视神经和视网膜的其他部位未见。在机械破坏血脑屏障后，脑内注射NMO-IgG也可见。对于对照（非NMO）IgG或AQP 4敲除小鼠中的NMO-IgG，未发现选择性细胞定位。直接注射到脑实质中的NMO-IgG在24小时内扩散超过1.5mm2的面积，并靶向星形胶质细胞足突。我们的数据建立了小鼠中的NMO-IgG药代动力学和组织分布。血清NMO-IgG在外周器官中而不是CNS中快速接近AQP 4表明限制性抗体接近不能解释外周器官中没有NMO病理学。
The pathogenesis of neuromyelitis optica (NMO) involves binding of IgG autoantibodies (NMO-IgG) to aquaporin-4 (AQP4) on astrocytes in the central nervous system (CNS). We studied the in vivo processing in mice of a recombinant monoclonal human NMO-IgG that binds strongly to mouse AQP4. Following intravenous administration, serum [NMO-IgG] decreased with t1/2 ∼18 hours in wildtype mice and ∼41 hours in AQP4 knockout mice. NMO-IgG was localized to AQP4-expressing cell membranes in kidney (collecting duct), skeletal muscle, trachea (epithelial cells) and stomach (parietal cells). NMO-IgG was seen on astrocytes in the area postrema in brain, but not elsewhere in brain, spinal cord, optic nerve or retina. Intravenously administered NMO-IgG was also seen in brain following mechanical disruption of the blood-brain barrier. Selective cellular localization was not found for control (non-NMO) IgG, or for NMO-IgG in AQP4 knockout mice. NMO-IgG injected directly into brain parenchyma diffused over an area of ∼5 mm2 over 24 hours and targeted astrocyte foot-processes. Our data establish NMO-IgG pharmacokinetics and tissue distribution in mice. The rapid access of serum NMO-IgG to AQP4 in peripheral organs but not the CNS indicates that restricted antibody access cannot account for the absence of NMO pathology in peripheral organs.
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影响因子：
11.2
作者：
Bennett, Jeffrey L.;Lam, Chiwah;Kalluri, Sudhakar Reddy;Saikali, Philippe;Bautista, Katherine;Dupree, Cecily;Glogowska, Magdalena;Case, David;Antel, Jack P.;Owens, Gregory P.;Gilden, Don;Nessler, Stefan;Stadelmann, Christine;Hemmer, Bernhard
通讯作者：
Hemmer, Bernhard
神经霉素炎患者Optica患者的Aquaporin-4结合自身抗体通过下调EAAT2损害谷氨酸的转运。
影响因子：
15.3
作者：
Hinson, Shannon R.;Roemer, Shanu F.;Lucchinetti, Claudia F.;Fryer, James P.;Kryzer, Thomas J.;Chamberlain, Jayne L.;Howe, Charles L.;Pittock, Sean J.;Lennon, Vanda A.
通讯作者：
Lennon, Vanda A.
影响因子：
5.8
作者：
Bonnan, M.;Valentino, R.;Cabre, P.
通讯作者：
Cabre, P.
影响因子：
4.8
作者：
Li, Lihua;Zhang, Hua;Verkman, A. S.
通讯作者：
Verkman, A. S.
DOI：
10.1016/j.bbrc.2010.02.157
发表时间：
2010-03-26
影响因子：
3.1
作者：
Kinoshita, Makoto;Nakatsuji, Yuji;Sakoda, Saburo
通讯作者：
Sakoda, Saburo