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Blood, 15 May 2001, Vol. 97, No. 10, pp. 3093-3099
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Effect of the PlA2 alloantigen on the function of
 3-integrins in platelets
Joel S. Bennett,
Francesca Catella-Lawson,
Andrew R. Rut,
Gaston Vilaire,
Weiwei Qi,
Shiv C. Kapoor,
Scott Murphy, and
Garret A. FitzGerald
From the Hematology-Oncology Division, the Center for
Experimental Therapeutics, and the General Clinical Research Center of
the University of Pennsylvania School of Medicine, Philadelphia,
Pennsylvania; SmithKline Beecham Pharmaceuticals, Harlow, United
Kingdom; and the Musser Blood Center, American Red Cross Blood
Services, Penn-Jersey Region, Philadelphia, Pennsylvania.
The polymorphism responsible for the PlA2 alloantigen
on the  3-component of 3-containing
integrins is reported to be a risk factor for coronary thrombosis. This
study examined the effect of PlA2 on the function of
3-integrins using platelets from subjects homozygous and
heterozygous for PlA1 and PlA2. There was
overlap in the distribution of the dissociation constant (Kd) and maximum fibrinogen binding (Bmax)
values for fibrinogen binding to  IIb3 on
platelets from PlA1 and PlA2 homozygotes and
PlA1/PlA2 heterozygotes. However, whereas there
was no statistical difference in these values for the PlA1
homozygotes and PlA2 heterozygotes, the Kd for
the PlA2 homozygotes was significantly lower than that for
the PlA1/PlA2 heterozygotes, but was not
statistically different from that for the PlA1 homozygotes.
No differences were detected in ADP sensitivity between platelets from
PlA1 homozygotes and PlA1/PlA2
heterozygotes, in the IC50 for RGDS inhibition of
fibrinogen binding to IIb3, in the
v3-mediated adhesion of platelets to
osteopontin and vitronectin, and in the phorbol ester-stimulated adhesion to fibrinogen of B lymphocytes expressing
IIb3 containing either the
PlA1 or the PlA2 polymorphism. Finally, no
differential effects of PlA2 on turbidometric platelet
aggregation, platelet secretion, or platelet thrombus formation were
found as measured in the PFA-100. Because no differences were detected
in the ability of 3-integrins to interact with ligands
based on the presence or absence of the PlA2 polymorphism,
the results suggest that factors unrelated to 3-integrin function may account for the reported association of the
PlA2 allele with coronary thrombosis.
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