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

ABSTRACT: 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? chain that interacted closely with a counterpart region on the ? chain in a soluble state. New anti-B? and anti-? 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.

SUBMITTER: Hisada Y 

PROVIDER: S-EPMC3764439 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature