INTERSPECIES COMPARISON OF PLATELET-AGGREGATION, LIBS EXPRESSION AND CLOT RETRACTION - OBSERVED DIFFERENCES IN GPIIB-IIIA FUNCTIONAL-ACTIVITY

We examined interspecies differences in the function of the platelet f ibrinogen receptor, GPIIb-IIIa, by comparing platelet aggregation resp onses to adenosine diphosphate (ADP) added alone or in combination wit h a GPIIIa specific monoclonal antibody (mAb), D3. D3 can activate the GPIIb-IIIa receptor in the absence of platelet activation, and it pre ferentially binds to a region on the GPIIIa subunit after the GPIlb-II Ia complex is occupied by ligand. Using human, monkey, dog, rabbit and pig platelets, we examined whether all species' platelets bound the D 3 mAb similarly, and if the binding of Arg-Gly-Asp-Ser (RGDS) peptides induced the exposure of the anti-LIES (D3) epitope as previously desc ribed for human platelets. We also evaluated how blocking of this neoa ntigenic region by the D3 mAb affected clot retraction, a process that requires linkage of GPIIb-IIIa with fibrin(ogen) and the platelet cyt oskeleton. We found that all species tested bound the D3 mAb. Only in human and monkey platelets did D3 cause aggregation as well as inhibit clot retraction. However, in all species tested, except for pig, D3 p revented disaggregation of platelets typically observed when platelets are treated with low dose ADP. With the exception of pig platelets, t here was increased D3 binding to platelets in the presence of RGDS pep tides. We propose that this region of GPIIIa is important in the confo rmational changes that GPIIb-IIIa undergoes during the binding of liga nd in most species tested. Our studies suggest 1) there are measurable inter-species differences in GPIIb-IIIa mediated platelet aggregation and clot retraction, 2) LIES expression due to receptor occupancy is a common but not all-inclusive response and 3) interspecies comparison s may be useful in understanding structural and functional aspects of platelet GPIIb-IIIa.