Veszelka Szilvia, Laszy Judit, Pázmány Tamás, Németh László, Obál Izabella, Fábián László, Szabó Gábor, Abrahám Csongor S, Deli Mária A, Urbányi Zoltán
Eur J Microbiol Immunol (Bp). 2013 Dec;3(4):281-9. doi: 10.1556/EuJMI.3.2013.4.8. Epub 2013 Nov 21.
Serum amyloid P component (SAP), a member of the innate immune system, does not penetrate the brain in physiological conditions; however, SAP is a stabilizing component of the amyloid plaques in neurodegenerative diseases. We investigated the cerebrovascular transport of human SAP in animal experiments and in culture blood-brain barrier (BBB) models. After intravenous injection, no SAP could be detected by immunohistochemistry or ELISA in healthy rat brains. Salmonella typhimurium lipopolysaccharide injection increased BBB permeability for SAP and the number of cerebral vessels labeled with fluorescein isothiocyanate (FITC)-SAP in mice. Furthermore, when SAP was injected to the rat hippocampus, a time-dependent decrease in brain concentration was seen demonstrating a rapid SAP efflux transport in vivo. A temperature-dependent bidirectional transport of FITC-SAP was observed in rat brain endothelial monolayers. The permeability coefficient for FITC-SAP was significantly higher in abluminal to luminal (brain to blood) than in the opposite direction. The luminal release of FITC-SAP from loaded endothelial cells was also significantly higher than the abluminal one. Our data indicate the presence of BBB efflux transport mechanisms protecting the brain from SAP penetration. Damaged BBB integrity due to pathological insults may increase brain SAP concentration contributing to development of neurodegenerative diseases.
血清淀粉样蛋白P成分（SAP）是先天性免疫系统的一员，在生理条件下不会穿透血脑屏障；然而，在神经退行性疾病中，SAP是淀粉样斑块的稳定成分。我们在动物实验和培养的血脑屏障（BBB）模型中研究了人SAP的脑血管转运情况。静脉注射后，在健康大鼠脑中通过免疫组织化学或酶联免疫吸附测定（ELISA）均未检测到SAP。注射鼠伤寒沙门氏菌脂多糖可增加小鼠血脑屏障对SAP的通透性以及用异硫氰酸荧光素（FITC）标记的SAP标记的脑血管数量。此外，当将SAP注射到大鼠海马体时，观察到脑内浓度呈时间依赖性下降，表明体内存在快速的SAP外流转运。在大鼠脑内皮单层细胞中观察到FITC-SAP的温度依赖性双向转运。FITC-SAP从管腔外到管腔（脑到血）的通透系数明显高于相反方向。负载内皮细胞中FITC-SAP的管腔释放也明显高于管腔外释放。我们的数据表明存在血脑屏障外流转运机制，可保护大脑免受SAP的穿透。由于病理损伤导致的血脑屏障完整性受损可能会增加脑内SAP浓度，从而促进神经退行性疾病的发展。
