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EI Peerschke
Department of Pathology, SUNY, Stony Brook 11794-7300.
Progressive decreases in platelet-bound fibrinogen accessibility to
antibody and enzymes were recently reported to occur after adenosine
diphosphate (ADP)-induced fibrinogen binding. Because previous studies also
indicated that platelets that are activated but not aggregated by ADP in
the presence of fibrinogen lose their ability to aggregate in a
time-dependent manner despite negligible changes in fibrinogen binding, the
present study examined the relationship between platelet aggregation and
accessibility of platelet-bound fibrinogen to specific polyclonal antibody
F(ab')2 fragments over a 60-minute time course. Although 125I-fibrinogen
binding remained virtually unchanged, comparison of antifibrinogen antibody
F(ab')2 binding and platelet aggregation 5 minutes and 60 minutes after
platelet stimulation with ADP or thrombin showed decreases in F(ab')2
binding of 62% +/- 13% and 73% +/- 7% (mean +/- SD, n = 5), respectively,
and decreases of 65% +/- 16% and 60% +/- 10% in platelet aggregation. In
contrast, platelets stimulated with A23187 or chymotrypsin retained 87% +/-
16% and 76% +/- 12% of their ability to aggregate over the same time
course, and lost only 39% +/- 14% and 36% +/- 12% of their ability to bind
antifibrinogen antibody F(ab')2 fragments, respectively. Pretreatment of
ADP-stimulated platelets with chymotrypsin largely prevented the
progressive loss of platelet aggregability and the accompanying decreased
recognition of bound fibrinogen by antifibrinogen F(ab')2 fragments.
Preincubation of platelets with cytochalasin D (30 micrograms/mL) also
inhibited the decrease in platelet aggregation after exposure of
ADP-treated platelets to fibrinogen over a 60-minute time course. This was
accompanied by only a 25% +/- 18% decrease in antifibrinogen antibody
F(ab')2 binding. Present data support the hypothesis that qualitative
changes in platelet-bound fibrinogen correlate with loss of the ability of
platelets to aggregate, and implicate both the platelet cytoskeleton and
chymotrypsin-sensitive surface membrane structures in modulating
qualitative changes in bound fibrinogen on the platelet surface.
This article has been cited by other articles:
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| Copyright © 1992 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||