Summary
Conformational activation of platelet GpIIb/IIIa which is coupled to increased affinity
for binding of soluble fibrinogen is an important step in platelet aggregation. Antibodies,
peptides, and small molecules which antagonise fibrinogen binding, therefore, have
been developed as a new class of potent anti-aggregatory compounds. The binding of
these artificial ligands, however, similar to fibrinogen binding may also stimulate
platelet adhesion and degranulation. Therefore, in this study effects of MK-852, a
cyclic hexapeptide based on the RGD-template, on the platelet phenotype were analysed
by whole blood flow cytometry. MK-852 already in the nanomolar range completely inhibited
the surface binding of fibrinogen to ADP or TRAP-6 stimulated platelets. In the micromolar
range, MK-852 induced an up to four-fold increase of GpIIb/IIIa surface expression
in the absence of increased P-selectin expression. In conclusion our results suggest
that the selective surface recruitment of GpIIb/IIIa may be a side effect of exposure
to RGD-analogues which occurs at concentrations well above inhibition of fibrinogen
binding.
