Stimulation of platelet glycoprotein IIb-IIIa (alpha IIb beta 3-integrin) functional activity by a monoclonal antibody to the N-terminal region of glycoprotein IIIa.
Platelet glycoprotein (GP) IIb-IIIa complex (alpha IIb beta 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 < or = 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.
Mazurov
A V
AV
Institute of Experimental Cardiology, Cardiology Research Center, Moscow, Russian Federation.
Khaspekova
S G
SG
Byzova
T V
TV
Tikhomirov OYu
Berndt
M C
MC
Steiner
B
B
Kouns
W C
WC
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D018955:CD36 Antigens / Q000276:immunology / Q000502:physiology*; D000939:Epitopes / Q000032:analysis; D005340:Fibrinogen / Q000494:pharmacology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000276:immunology / Q000502:physiology*; D011487:Protein Conformation
D000911:Antibodies, Monoclonal; D018955:CD36 Antigens; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D009842:Oligopeptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C047981:arginyl-glycyl-aspartic acid; D005340:Fibrinogen; C059453:RGES peptide; C046617:arginyl-glycyl-aspartyl-serine