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Internalization of bound fibrinogen modulates platelet aggregation
JD Wencel-Drake, C Boudignon-Proudhon, MG Dieter, AB Criss and LV Parise
Department of Medical Laboratory Sciences, University of Illinois at
Chicago 60612, USA.
In agonist-stimulated platelets, the integrin alpha IIb beta 3
(glycoprotein IIb-IIIa) is converted from an inactive to an active
fibrinogen receptor, thereby mediating platelet aggregation. With time
after agonist addition, at least two events occur: fibrinogen becomes
irreversibly bound to the platelet and, when stirring is delayed, platelets
lose the ability to aggregate despite the presence of maximally bound
fibrinogen. Because we previously identified an actively internalized pool
of alpha IIb, beta 3 in platelets, we explored the possibility that both of
these events might result from the internalization of fibrinogen bound to
active alpha IIb beta 3. Under conditions of irreversible fibrinogen
binding, fluorescence microscopy showed that biotinylated fibrinogen is
rapidly internalized by activated platelets to a surface-inaccessible,
intracellular pool. Flow cytometric analysis showed that the observed loss
in accessibility to extracellular probes immediately precedes a loss in
ability to the platelets to aggregate. Moreover, prevention of irreversible
fibrinogen binding results in a prevention of internalization and a
retention of aggregation capacity. Thus, the internalization of fibrinogen
from the activated platelet surface appears to contribute not only to the
irreversible phase of fibrinogen binding, but also to the downregulation of
platelet adhesiveness. Fibrinogen internalization is therefore likely to
represent a fundamental regulatory mechanism that modulates platelet
function.
Volume 87,
Issue 2,
pp. 602-612,
01/15/1996
Copyright © 1996 by The American Society of Hematology
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