Myrsky Essi, Caja Sergio, Simon-Vecsei Zsofi, Korponay-Szabo Ilma R, Nadalutti Cristina, Collighan Russell, Mongeot Alexandre, Griffin Martin, Mäki Markku, Kaukinen Katri, Lindfors Katri
Pediatric Research Center, Medical School, University of Tampere, Tampere, Finland.
Cell Mol Life Sci. 2009 Oct;66(20):3375-85. doi: 10.1007/s00018-009-0116-1. Epub 2009 Aug 13.
Celiac disease is characterized by the presence of specific autoantibodies targeted against transglutaminase 2 (TG2) in untreated patients' serum and at their production site in the small-bowel mucosa below the basement membrane and around the blood vessels. As these autoantibodies have biological activity in vitro, such as inhibition of angiogenesis, we studied if they might also modulate the endothelial barrier function. Our results show that celiac disease patient autoantibodies increase endothelial permeability for macromolecules, and enhance the binding of lymphocytes to the endothelium and their transendothelial migration when compared to control antibodies in an endothelial cell-based in vitro model. We also demonstrate that these effects are mediated by increased activities of TG2 and RhoA. Since the small bowel mucosal endothelium serves as a "gatekeeper" in inflammatory processes, the disease-specific autoantibodies targeted against TG2 could thus contribute to the pathogenic cascade of celiac disease by increasing blood vessel permeability.
乳糜泻的特征是未经治疗的患者血清中存在针对转谷氨酰胺酶2（TG2）的特异性自身抗体，且在基底膜下方和血管周围的小肠黏膜中的产生部位也有这些抗体。由于这些自身抗体在体外具有生物学活性，如抑制血管生成，我们研究了它们是否也可能调节内皮屏障功能。我们的结果表明，在基于内皮细胞的体外模型中，与对照抗体相比，乳糜泻患者的自身抗体增加了大分子的内皮通透性，并增强了淋巴细胞与内皮的结合及其跨内皮迁移。我们还证明，这些作用是由TG2和RhoA活性增加介导的。由于小肠黏膜内皮在炎症过程中起“守门人”作用，因此针对TG2的疾病特异性自身抗体可能通过增加血管通透性而促成乳糜泻的致病级联反应。
