Premium
Stimulation of platelet glycoprotein IIb‐IIIa (α IIb β 3 ‐integrin) functional activity by a monoclonal antibody to the N‐terminal region of glycoprotein IIIa
Author(s) -
Mazurov Alexey V.,
Khaspekova Svetlana G.,
Byzova Tatjana V.,
Tikhomirov Oleg Yu.,
Berndt Michael C.,
Steiner Beat,
Kouns William C.
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(96)00709-0
Subject(s) - epitope , chemistry , monoclonal antibody , platelet , glycoprotein , platelet activation , integrin , fibrinogen , microbiology and biotechnology , platelet membrane glycoprotein , antibody , binding site , epitope mapping , biochemistry , immunology , biology , cell
Platelet glycoprotein (GP) IIb‐IIIa complex (α IIb β 3 ‐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.