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The Arg-Gly-Asp (RGD) recognition site of platelet glycoprotein IIb- IIIa
on nonactivated platelets is accessible to high-affinity macromolecules
Y Tomiyama, T Tsubakio, RS Piotrowicz, Y Kurata, JC Loftus and TJ Kunicki
Blood Center of Southeastern Wisconsin, Milwaukee 53233.
We have characterized a murine IgG monoclonal antibody, OP-G2, specific for
platelet glycoprotein (GP) IIb-IIIa (alpha IIb beta 3). OP-G2 Fab fragments
inhibit fibrinogen-mediated platelet aggregation and competitively inhibit
adenosine diphosphate-induced binding of 125I- fibrinogen to washed
platelets. OP-G2 binding to GPIIb-IIIa is specifically inhibited by
RGD-containing peptides but not the fibrinogen gamma-chain carboxy-terminal
peptide, and OP-G2 Fab fragments, like RGD-containing peptides, alter the
conformation of GPIIb-IIIa resulting in the expression of a ligand-induced
binding site (LIBS) recognized by PMI-1. OP-G2 fails to bind to the
recombinant Cam variant of GPIIb-IIIa (alpha III beta 3Cam) wherein an
Asp119 to Tyr119 substitution in GPIIIa abrogates the ability to recognize
RGD. These data indicate that OP-G2 recognizes an epitope at or in very
close proximity to the RGD recognition site of GPIIb-IIIa and that, in
every aspect tested, OP-G2 behaves like a macromolecular RGD ligand.
Interestingly, two-color flow cytometry shows that OP-G2 IgG can bind to
nonactivated platelets. Quantitative binding assays indicate that
nonactivated platelets bind approximately 50,000 125I-OP-G2
molecules/platelet. Furthermore, the affinity of OP-G2 for platelets
activated with thrombin is roughly fivefold higher (nonactivated, kd = 24.8
nmol/L; activated, kd = 4.9 nmol/L). These results suggest that the RGD
recognition site of GPIIb-IIIa is available to macromolecules that contain
RGD even on nonactivated platelets, provided that the affinity of the
ligand is adequate.
Volume 79,
Issue 9,
pp. 2303-2312,
05/01/1992
Copyright © 1992 by The American Society of Hematology
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