Stimulation of platelet glycoprotein IIb‐IIIa (αIIbβ3‐integrin) functional activity by a monoclonal antibody to the N‐terminal region of glycoprotein IIIa

FEBS Letters

Steiner, Beat²  Tikhomirov, Oleg Yu.¹  Byzova, Tatjana V.¹  Mazurov, Alexey V.¹  Khaspekova, Svetlana G.¹  Kouns, William C.²  Berndt, Michael C.³ 

[1] Institute of Experimental Cardiology, Cardiology Research Center, Moscow, Russian Federation;F. Hoffmann La-Roche Ltd., Pharma Research, Basel, Switzerland;Baker Medical Research Institute, Prahran, Vic., Australia

关键词: Integrin;    Glycoprotein IIb-IIIa;    Conformation;    Fibrinogen;    Platelets;    GP;    glycoprotein;    LIBS;    ligand-induced binding site;    PRP;    platelet-rich plasma;    PBS;    phosphate-buffered saline;    monAB;    monoclonal antibody;   

DOI  :  10.1016/0014-5793(96)00709-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Platelet glycoprotein (GP) IIb-IIIa complex (α_IIbβ₃-integrin) changes its conformation upon platelet activation that results in binding of RGD-containing ligands and expression of ligand-induced binding site (LIBS) neoepitopes. Anti-GIIb-IIIa monoclonal antibody (monAB) CRC54 bound to ≤10% of GPIIb-IIIa on resting platelets but binding was enhanced by the occupation of GPIIb-IIIa with RGDS peptide and by platelet activation indicating that CRC54 is directed against LIBS epitope. The epitope was located within the first 100 N-terminal residues of GPIIIa and differed from other LIBS epitopes. CRC54 as well as its Fab fragments were able to induce platelet aggregation. CRC54 also stimulated interaction of GPIIb-IIIa with its ligands (fibrinogen and fibronectin) and conformation-dependent antibodies. The results indicated that changes of GPIIb-IIIa conformation, binding of ligands and platelet aggregation could be stimulated via interaction of anti-LIBS antibody with the N-terminal part of GPIIIa.

【 授权许可】

Unknown