Discovery of an uncovered region in fibrin clots and its clinical significance

作者：Hisada Yohei; Yasunaga Masahiro; Hanaoka Shingo; Saijou Shinji; Sugino Takashi; Tsuji Atsushi; Saga Tsuneo; Tsumoto Kouhei; Manabe Shino; Kuroda Jun ichiro; Kuratsu Jun ichi; Matsumura Yasuhiro^*

来源：Scientific Reports, 2013, 3(1): 2604.

DOI：10.1038/srep02604

Despite the pathological importance of fibrin clot formation, little is known about the structure of these clots because X-ray and nuclear magnetic resonance (NMR) analyses are not applicable to insoluble proteins. In contrast to previously reported anti-fibrin monoclonal antibodies (mAbs), our anti-fibrin clot mAb (clone 102-10) recognises an uncovered region that is exposed only when a fibrin clot forms. The epitope of the 102-10 mAb was mapped to a hydrophobic region on the B beta chain that interacted closely with a counterpart region on the gamma chain in a soluble state. New anti-B beta and anti-gamma mAbs specific to peptides lining the discovered region appeared to bind exclusively to fibrin clots. Furthermore, the radiolabelled 102-10 mAb selectively accumulated in mouse spontaneous tumours, and immunohistochemistry using this mAb revealed greater fibrin deposition in World Health Organization (WHO) grade 4 glioma than in lower-grade gliomas. Because erosive tumours are apt to cause micro-haemorrhages, even early asymptomatic tumours detected with a radiolabelled 102-10 mAb may be aggressively malignant.

• 出版日期2013-9-6
• 单位河北医科大学