High shear-dependent loss of membrane integrity and defective platelet adhesion following disruption of the GPIba-filamin interaction

Susan Cranmer, Katrina Ashworth, Yu Yao, Michael Claude Berndt, Zaverio M Ruggeri, Robert Andrews, Shaun Jackson

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68 Citations (Scopus)

Abstract

Our study demonstrates that the link between platelet GPIb and the cytoskeleton does not alter the intrinsic ligand binding function of GPIb or the ability of the receptor to stimulate integrin IIb 3-dependent spreading. However, exposure of hGPIb FW platelets to pathologic shear rate levels (5000 to 40 000 s 1) leads to the development of unstable membrane tethers, defective platelet adhesion, and loss of membrane integrity, leading to complete disintegration of the platelet cell body. These outcomes suggest that the GPIb filamin interaction not only regulates the architecture of the membrane skeleton, but also maintains the mechanical stability of the plasma membrane under conditions of high shear
Original languageEnglish
Pages (from-to)2718 - 2727
Number of pages10
JournalBlood
Volume117
Issue number9
DOIs
Publication statusPublished - 2011

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