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The activation-induced decrease in the platelet surface expression of the
glycoprotein Ib-IX complex is reversible
AD Michelson, SE Benoit, MH Kroll, JM Li, MJ Rohrer, AS Kestin and MR Barnard
Department of Pediatrics, University of Massachusetts Medical School,
Worcester 01655.
Thrombin decreases the platelet surface expression of the glycoprotein (GP)
Ib-IX complex. To determine whether this effect is reversible, flow
cytometric studies were performed with GPIb-IX-specific monoclonal
antibodies. In both whole blood and washed platelet systems, incubation of
platelets with thrombin or a combination of adenosine diphosphate and
epinephrine resulted in a maximal decrease of the platelet surface
expression of GPIb-IX within 5 minutes, after which there was a time-
dependent return of the platelet surface GPIb-IX complex, which was maximal
by 60 minutes. Exposure of the same platelets to additional exogenous
thrombin resulted in a second decrease in platelet surface GPIb-IX,
followed by a second reconstitution of platelet surface GPIb- IX.
Throughout these experiments there was no measurable release from the
platelets of glycocalicin (a proteolytic fragment of GPIb). Experiments in
which platelets were preincubated with a biotinylated GPIb-specific MoAb
showed that the GPIb molecules that returned to the platelet surface were
the same molecules that had been translocated to the intraplatelet pool.
The GPIb molecules that returned to the platelet surface were functionally
competent to bind von Willebrand factor, as determined by
ristocetin-induced platelet agglutination and ristocetin-induced binding of
exogenous von Willebrand factor. Inhibitors of protein kinase C and myosin
light-chain kinase enhanced the reexpression of platelet surface GPIb. In
summary, the activation- induced decrease in the platelet surface
expression of the GPIb-IX complex is reversible. Inactivation of protein
kinase C and myosin light-chain kinase are important mechanisms in the
reexpression of the platelet surface GPIb-IX complex.
Volume 83,
Issue 12,
pp. 3562-3573,
06/15/1994
Copyright © 1994 by The American Society of Hematology

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