在类风湿性关节炎小鼠模型中，骨桥蛋白内隐蔽表位SLAYGLR的重要作用。
Essential role of the cryptic epitope SLAYGLR within osteopontin in a murine model of rheumatoid arthritis.
作者信息
Yamamoto Nobuchika, Sakai Fumihiko, Kon Shigeyuki, Morimoto Junko, Kimura Chiemi, Yamazaki Harumi, Okazaki Ikuko, Seki Nobuo, Fujii Takashi, Uede Toshimitsu
机构信息
Exploratory Research Laboratories, Fujisawa Pharmaceutical Co, Ibaraki, Japan.
出版信息
J Clin Invest. 2003 Jul;112(2):181-8. doi: 10.1172/JCI17778.
It has been shown that osteopontin (OPN) plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA). However, the molecular mechanism of OPN action is yet to be elucidated. Splenic monocytes obtained from arthritic mice exhibited a significant capacity for cell migration toward thrombin-cleaved OPN but not toward full-length OPN. Migratory monocytes expressed alpha9 and alpha4 integrins. Since cleavage of OPN by thrombin exposes the cryptic epitope recognized by alpha9 and alpha4 integrins, we investigated the role of the cryptic epitope SLAYGLR in a murine RA model by using a specific antibody (M5) reacting to SLAYGLR sequence. The M5 antibody could abrogate monocyte migration toward the thrombin-cleaved form of OPN. Importantly, M5 antibody could inhibit the proliferation of synovium, bone erosion, and inflammatory cell infiltration in arthritic joints. Thus, we demonstrated that a cryptic epitope, the SLAYGLR sequence of murine OPN, is critically involved in the pathogenesis of a murine model of RA.
已有研究表明，骨桥蛋白（OPN）在类风湿关节炎（RA）的发病机制中起关键作用。然而，OPN作用的分子机制尚待阐明。从患关节炎小鼠获得的脾单核细胞对凝血酶切割的OPN表现出显著的细胞迁移能力，但对全长OPN则无此能力。迁移的单核细胞表达α9和α4整合素。由于凝血酶对OPN的切割暴露了α9和α4整合素识别的隐蔽表位，我们通过使用与SLAYGLR序列反应的特异性抗体（M5），在小鼠RA模型中研究了隐蔽表位SLAYGLR的作用。M５抗体可消除单核细胞向凝血酶切割形式的OPN的迁移。重要的是，M5抗体可抑制关节炎关节滑膜的增殖、骨侵蚀和炎性细胞浸润。因此，我们证明了一个隐蔽表位，即小鼠OPN的SLAYGLR序列，在小鼠RA模型的发病机制中起关键作用。
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