Specific synergy of multiple substrate-receptor interactions in platelet thrombus formation under flow.

Abstract:

:We have used confocal videomicroscopy in real time to delineate the adhesive interactions supporting platelet thrombus formation on biologically relevant surfaces. Type I collagen fibrils exposed to flowing blood adsorb von Willebrand factor (vWF), to which platelets become initially tethered with continuous surface translocation mediated by the membrane glycoprotein Ib alpha. This step is essential at high wall shear rates to allow subsequent irreversible adhesion and thrombus growth mediated by the integrins alpha2beta1 and alpha(IIb)beta3. On subendothelial matrix, endogenous vWF and adsorbed plasma vWF synergistically initiate platelet recruitment, and alpha2beta1 remains key along with alpha(IIb)beta3 for normal thrombus development at all but low shear rates. Thus, hemodynamic forces and substrate characteristics define the platelet adhesion pathways leading to thrombogenesis.

journal_name

Cell

journal_title

Cell

authors

Savage B,Almus-Jacobs F,Ruggeri ZM

doi

10.1016/s0092-8674(00)81607-4

subject

Has Abstract

pub_date

1998-09-04 00:00:00

pages

657-66

issue

5

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(00)81607-4

journal_volume

94

pub_type

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