Activation and shedding of platelet glycoprotein IIb/IIIa under non-physiological shear stress
- 386 Downloads
The purpose of this study was to investigate the influence of non-physiological high shear stress on activation and shedding of platelet GP IIb/IIIa receptors. The healthy donor blood was exposed to three levels of high shear stresses (25, 75, 125 Pa) from the physiological to non-physiological status with three short exposure time (0.05, 0.5, 1.5 s), created by a specific blood shearing system. The activation and shedding of the platelet GPIIb/IIIa were analyzed using flow cytometry and enzyme-linked immunosorbent assay. In addition, platelet P-selectin expression of sheared blood, which is a marker for activated platelets, was also analyzed. The results from the present study showed that the number of activated platelets, as indicated by the surface GPIIb/IIIa activation and P-selectin expression, increased with increasing the shear stress level and exposure time. However, the mean fluorescence of GPIIb/IIIa on the platelet surface, decreased with increasing the shear stress level and exposure time. The reduction of GPIIb/IIIa on the platelet surface was further proved by the reduction of further activated platelet GPIIb/IIIa surface expression induced by ADP and the increase in GPIIb/IIIa concentration in microparticle-free plasma with increasing the applied shear stress and exposure time. It is clear that non-physiological shear stress induce a paradoxical phenomenon, in which both activation and shedding of the GPIIb/IIIa on the platelet surface occur simultaneously. This study may offer a new perspective to explain the reason of both increased thrombosis and bleeding events in patients implanted with high shear blood-contacting medical devices.
KeywordsGlycoprotein IIb/IIIa (Integrin αIIb/β3) Blood-contacting medical devices Non-physiological shear stress Shear-induced hemostatic dysfunction Shear-induced platelet activation
This work was partially supported by the National Institutes of Health (Grant numbers: R01 HL 088100, R01 HL124170) and the International Postdoctoral Exchange Fellowship Program (No. 20130028).
Compliance with Ethical Standards
Conflict of interest
The authors declared that there are no conflicts of interests.
- 2.National Kidney Foundation (2012) The facts about chronic kidney disease. National Kidney Foundation, New YorkGoogle Scholar
- 21.Reddy KB, Smith DM, Plow EF (2008) Analysis of Fyn function in hemostasis and alphaIIbbeta3-integrin signaling. J Cell Sci 15:1211641–1211648Google Scholar
- 29.Nesbitt WS, Kulkarni S, Giuliano S, Goncalves I, Dopheide SM, Yap CL, Harper IS, Salem HH, Jackson SP (2002) Distinct glycoprotein Ib/V/IX and integrin alpha(IIb)beta(3)-dependent calcium signals cooperatively regulate platelet adhesion under flow. J Biol Chem 277:2965–2972CrossRefPubMedGoogle Scholar