The activation-induced decrease in the platelet surface expression of the glycoprotein Ib-IX complex is reversible.
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.
Michelson
A D
AD
Department of Pediatrics, University of Massachusetts Medical School, Worcester 01655.
Benoit
S E
SE
Kroll
M H
MH
Li
J M
JM
Rohrer
M J
MJ
Kestin
A S
AS
Barnard
M R
MR
D000328:Adult; D001792:Blood Platelets / Q000378:metabolism*; D006801:Humans; D015539:Platelet Activation; D010980:Platelet Membrane Glycoproteins / Q000032:analysis* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000032:analysis*; D013917:Thrombin / Q000494:pharmacology; D014841:von Willebrand Factor / Q000378:metabolism
D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D014841:von Willebrand Factor; C028254:von Willebrand factor receptor; D013917:Thrombin