In vivo distribution of β2 glycoprotein I under various pathophysiologic conditions
In vivo distribution of β2 glycoprotein I under various pathophysiologic conditions
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DOI：
10.1182/blood-2011-01-333617
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发表时间：
2011-10-13
期刊：
影响因子：
20.3
通讯作者：
Tedesco, Francesco
中科院分区：
文献类型：
--
作者：
Agostinis, Chiara;Biffi, Stefania;Tedesco, Francesco
体外研究已经证明，使用抗磷脂抗体，β 2糖蛋白I（β 2GPI）与内皮细胞（EC）和滋养层结合。尚未研究β 2GPI与这些细胞的体内结合以及有利于它们相互作用的条件。我们分析了花青5.5标记的β 2GPI在小鼠体内的分布，并评估了妊娠和循环抗体对其组织定位的影响。通过全身扫描和离体分析在肝脏中检测信号。β 2GPI不能与血管内皮结合，仅与子宫血管内皮细胞反应。在妊娠小鼠中，该蛋白定位于胚胎着床部位的EC和滋养层。免疫小鼠显示出与未免疫小鼠相似的β 2GPI生物分布，但免疫妊娠动物显示出与着床部位C3和C9沉积相关的胎儿丢失显著增加。在注射β 2GPI-Cy 5.5后用LPS处理小鼠促进了免疫小鼠中与IgG、C1 q和C9沉积相关的肠和脑EC上的蛋白定位。这些发现表明，β 2GPI结合EC需要启动促炎因子，这是不需要的子宫和胎盘定位可能依赖于激素的变化。（血。2011;118（15）：4231-4238）
In vitro studies have documented beta 2 glycoprotein I (beta 2GPI) binding to endothelial cells (ECs) and trophoblast using antiphospholipid antibodies. The in vivo binding of beta 2GPI to these cells and the conditions that favor their interaction have not been investigated. We analyzed the in vivo distribution of cyanine 5.5-labeled beta 2GPI in mice and evaluated the effect of pregnancy and circulating antibodies on its tissue localization. The signal was detected in the liver by whole body scan and ex vivo analysis. The beta 2GPI failed to bind to the vascular endothelium and reacted only with the ECs of uterine vessels. In pregnant mice the protein was localized on ECs and trophoblast at the embryo implantation sites. Immunized mice showed a similar beta 2GPI biodistribution to naive mice but the immunized pregnant animals exhibited a significant increase in fetal loss associated with C3 and C9 deposition at the implantation sites. Treatment of mice with LPS after beta 2GPI-Cy5.5 injection promoted protein localization on gut and brain ECs associated with IgG, C1q, and C9 deposition in immunized mice. These findings indicate that beta 2GPI binding to EC requires priming with pro-inflammatory factors which is not needed for uterine and placental localization probably dependent on hormonal changes. (Blood. 2011;118(15):4231-4238)