Linked Life Data

20696943

Source:http://linkedlifedata.com/resource/pubmed/id/20696943

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2010-11-12
pubmed:abstractText
The function of the mechanosensitive, multimeric blood protein von Willebrand factor (VWF) is dependent on its size. We tested the hypothesis that VWF may self-associate on the platelet glycoprotein Ib? (GpIb?) receptor under hydrodynamic shear. Consistent with this proposition, whereas Alexa-488-conjugated VWF (VWF-488) bound platelets at modest levels, addition of unlabeled VWF enhanced the extent of VWF-488 binding. Recombinant VWF lacking the A1-domain was conjugated with Alexa-488 to produce ?A1-488. Although ?A1-488 alone did not bind platelets under shear, this protein bound GpIb? on addition of either purified plasma VWF or recombinant full-length VWF. The extent of self-association increased with applied shear stress more than ? 60 to 70 dyne/cm(2). ?A1-488 bound platelets in the milieu of plasma. On application of fluid shear to whole blood, half of the activated platelets had ?A1-488 bound, suggesting that VWF self-association may be necessary for cell activation. Shearing platelets with 6-?m beads bearing either immobilized VWF or anti-GpIb? mAb resulted in cell activation at shear stress down to 2 to 5 dyne/cm(2). Taken together, the data suggest that fluid shear in circulation can increase the effective size of VWF bound to platelet GpIb? via protein self-association. This can trigger mechanotransduction and cell activation by enhancing the drag force applied on the cell-surface receptor.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1528-0020
pubmed:author
pubmed:issnType
Electronic
pubmed:day
11
pubmed:volume
116
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3990-8
pubmed:dateRevised
2011-11-14
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
von Willebrand factor self-association on platelet GpIbalpha under hydrodynamic shear: effect on shear-induced platelet activation.
pubmed:affiliation
Chemical and Biological Engineering, State University of New York, Buffalo, NY 14260, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, N.I.H., Extramural