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Increased surface expression of the membrane glycoprotein IIb/IIIa complex
induced by platelet activation. Relationship to the binding of fibrinogen
and platelet aggregation
K Niiya, E Hodson, R Bader, V Byers-Ward, JA Koziol, EF Plow and ZM Ruggeri
Platelet activation altered the binding of three monoclonal antibodies
(monovalent Fab' fragment) directed against the glycoprotein (GP) IIb/IIIa
complex. An increased binding of two- to threefold occurred after
stimulation with thrombin or phorbol myristate acetate (PMA), with slight
but significant increase in the dissociation constants (Kd) of two
antibodies (LJ-CP8 and LJ-P9). In contrast, no statistically significant
changes were observed with ADP-stimulated platelets. The increased binding
of LJ-CP3, but not of the other two antibodies, to activated platelets
decreased by 30% to 40% in the presence of EDTA at 22 to 25 degrees C.
Platelets stimulated by thrombin or PMA bound more fibrinogen than did
those stimulated by ADP, and significant differences in the extent but not
in the affinity of fibrinogen binding were observed with various platelet
agonists. When the pool of GP IIb/IIIa molecules exposed on the surface of
unstimulated platelets was reacted with the monoclonal antibody LJ-CP3 to
block ADP-induced fibrinogen binding and platelet aggregation, stimulation
with thrombin or PMA still induced substantial binding of antibody and
fibrinogen, and aggregation ensued. Therefore, platelets exposed to
"strong" agonists exhibit an increased number of surface-oriented epitopes
associated with GP IIb/IIIa. The GP IIb/IIIa molecules bearing these newly
exposed epitopes are functional in that they can bind fibrinogen and
mediate platelet aggregation.
Volume 70,
Issue 2,
pp. 475-483,
08/01/1987
Copyright © 1987 by The American Society of Hematology

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