| Autor: |
Wencel-Drake, June D., Boudignon-Proudhon, Christel, Dieter, Michael G., Criss, Anne B., Parise, Leslie V. |
| Zdroj: |
Blood; January 1996, Vol. 87 Issue: 2 p602-612, 11p |
| Abstrakt: |
In agonist-stimulated platelets, the integrin αIIbβ3(glycoprotein lIb-lIIa) 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 αIIbβ3in platelets, we explored the possibility that both of these events might result from the internalization of fibrinogen bound to active αIIbβ3. 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 of 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. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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