This study investigates three aspects of the adhesive interaction operating between platelet glycoprotein Ib/IX and integrin αIIbβ3. These include the following: 1) examining the sufficiency of GPIb/IX and integrin αIIbβ3 to mediate irreversible cell adhesion on immobilized von Willebrand factor (vWf) under flow; 2) the ability of the vWf-GPIb interaction to induce integrin αIIbβ3 activation independent of endogenous platelet stimuli; and 3) the identification of key second messengers linking the vWf-GPIb/IX interaction to integrin αIIbβ3 activation. By using Chinese hamster ovary cells transfected with GPIb/IX and integrin αIIbβ3, we demonstrate that these receptors are both necessary and sufficient to mediate irreversible cell adhesion under flow, wherein GPIb/IX mediates cell tethering and rolling on immobilized vWf, and integrin αIIbβ3 mediates cell arrest. Moreover, we demonstrate direct signaling between GPIb/IX and integrin αIIbβ3. Studies on human platelets demonstrated that vWf binding to GPIb/IX is able to induce integrin αIIbβ3 activation independent of endogenous platelet stimuli under both static and physiological flow conditions (150-1800 s-1). Analysis of the key second messengers lingking the vWf-GPIb interaction to integrin αIIbβ3 activation demonstrated that the first step in the activation process involves calcium release from internal stores, whereas transmembrane calcium influx is a secondary event potentiating integrin αIIbβ3 activation.
CITATION STYLE
Yap, C. L., Hughan, S. C., Cranmer, S. L., Nesbitt, W. S., Rooney, M. M., Giuliano, S., … Jackson, S. P. (2000). Synergistic adhesive interactions and signaling mechanisms operating between platelet glycoprotein Ib/IX and integrin αIIbβ3: Studies in human platelets and transfected Chinese hamster ovary cells. Journal of Biological Chemistry, 275(52), 41377–41388. https://doi.org/10.1074/jbc.M005590200
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