Triflavin, an Arg-Gly-Asp-containing disintegrin,binds to resting- and activated-IIb3 integrin

• Main Authors: He-Nan Huang, 黃河南
• Other Authors: Ching-Hsiang Wu
• Format: Others
• Language: zh-TW
• Published: 2000
• Online Access: http://ndltd.ncl.edu.tw/handle/20570430405376082983

碩士 === 台北醫學院 === 醫學研究所 === 88 === The platelet membrane glycoprotein (GP) IIb/IIIa complex is a calcium-dependent heterodimer that serves as a receptor for adhesion molecules, and mediates platelet adhesion and aggregation. It inhibits platelet aggregation by interfering with the interaction of fibrinogen with the GP IIb/IIIa complex. In our previous report, triflavin was bound to the GP IIb/IIIa complex of resting and activated platelets with a similar binding affinity. The binding sites of triflavin at the subcellular structures of the platelets remain unclear. In the present study, washed human platelets were treated with triflavin for binding to GP IIb/IIIa complex, and the ligand-receptor complexes were then revealed by immunoEM techniques with anti-triflavin. Consequently, we provided the first morphological evidences to show the specific binding of triflavin with GP IIb/IIIa complex on both resting and collagen-activated platelets. The latters however did not be influenced in their ultrastructures after the binding of triflavin. In such circumstance, the triflavin-GP IIb/IIIa complexes of both resting- and stimulated-platelets were localized at the surface membrane, the plasma membrane of the open canalicular system (OCS) and the dense tubular system (DTS). Moreover, the present study also demonstrated a similar internalization of the triflavin-GP IIb/IIIa complexes on both resting and collagen-activated platelets, the complexes of which could be internalized from the surface plasma membrane into their open canalicular system and dense tubular system. Remarkably, in both resting and activated platelets, the triflavin-GP IIb/IIIa complexes could not be delivered into -granules where GP IIb/IIIa could not also be bound with triflavin in the fixed platelets of either quiescent or activated stage. The endocytosis of platelets was not affected following the binding of triflavin with GP IIb/IIIa complex as revealed by a tracer, HRP, which followed the usual endocytotic pathway to incorporate into the open canalicular system, vacuoles and granule-like structures with sizes similar to -granules. The present results therefore suggested that triflavin impeded platelet aggregation through simply occupying the binding sites of GP IIb/IIIa complex, nevertheless, the latter event did not cause observed changes of ultrastructures and normal physical functions in either resting or activated platelets.