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Evaluation of the role of platelet integrins in fibronectin‐dependent spreading and adhesion
Author(s) -
Mccarty O. J. T.,
Zhao Y.,
Andrew N.,
Machesky L. M.,
Staunton D.,
Frampton J.,
Watson S. P.
Publication year - 2004
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2004.00925.x
Subject(s) - fibronectin , integrin , lamellipodium , filopodia , microbiology and biotechnology , chemistry , platelet , tyrosine phosphorylation , platelet adhesiveness , adhesion , von willebrand factor , phosphorylation , extracellular matrix , biochemistry , immunology , biology , cell migration , receptor , in vitro , platelet aggregation , actin , organic chemistry
Summary. Background: Recent studies have shown that platelet adhesion and subsequent aggregation can occur in vivo in the absence of the two principal platelets adhesive ligands, von Willebrand factor and fibrinogen. These results highlight a possible role for fibronectin in supporting thrombus formation. Objective and methods: To evaluate the platelet integrins and subsequent activation pathways associated with fibronectin‐dependent platelet adhesion utilizing both human and murine platelets. Results: Platelets can adhere to fibronectin via the integrin α IIb β 3 , leading to formation of lamellipodia. This is mediated through an interaction with the tenth type III domain in fibronectin. Spreading on fibronectin promotes α IIb β 3 ‐mediated Ca 2+ mobilization and tyrosine phosphorylation of focal adhesion kinase and phospholipase C γ2. In contrast, studies with blocking antibodies and mice demonstrate that α 5 β 1 and α v β 3 support adhesion and promote formation of filopodia but not lamellipodia or tyrosine phosphorylation of these proteins. Further, neither α 5 β 1 nor α v β 3 is able to induce formation of lamellipodia in the presence of platelets agonists, such as collagen‐related‐peptide (CRP). Conclusions: These observations demonstrate that integrins α 5 β 1 and α v β 3 support platelet adhesion and the generation of filopodia but that, in contrast to the integrin α IIb β 3 , are unable to promote formation of lamellipodia.