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Amplification of bacteria-induced platelet activation is triggered by FcγRIIA, integrin αiIbβ3, and platelet factor 4

Arman, Mònica; Krauel, Krystin; Tilley, Dorothea O.; Weber, Claudia; Cox, Dermot; Greinacher, Andreas; Kerrigan, Steven W.; Watson, Steve P.

Authors

Mònica Arman

Krystin Krauel

Dorothea O. Tilley

Claudia Weber

Dermot Cox

Andreas Greinacher

Steven W. Kerrigan

Steve P. Watson



Abstract

Bacterial adhesion to platelets is mediated via a range of strain-specific bacterial surface proteins that bind to a variety of platelet receptors. It is unclear how these interactions lead to platelet activation. We demonstrate a critical role for the immune receptor FcγRIIA, αIIbβ3, and Src and Syk tyrosine kinases in platelet activation by Staphylococcus aureus, Streptococcus sanguinis, Streptococcus gordonii, Streptococcus oralis, and Streptococcus pneumoniae. FcγRIIA activation is dependent on immunoglobulin G (IgG) and αIIbβ3 engagement. Moreover, feedback agonists adenosine 59-diphosphate and thromboxane A2 aremandatory for platelet aggregation. Additionally, platelet factor 4 (PF4) binds to bacteria and reduces the lag time for aggregation, and gray platelet syndromea-granule-deficient platelets do not aggregate to 4 of 5 bacterial strains. We propose that FcγRIIA-mediated activation is a common response mechanism used against a wide range of bacteria, and that release of secondary mediators and PF4 serve as a positive feedback mechanism for activation through an IgG-dependent pathway. © 2014 by The American Society of Hematology.

Citation

Arman, M., Krauel, K., Tilley, D. O., Weber, C., Cox, D., Greinacher, A., …Watson, S. P. (2014). Amplification of bacteria-induced platelet activation is triggered by FcγRIIA, integrin αiIbβ3, and platelet factor 4. Blood, 123(20), 3166-3174. https://doi.org/10.1182/blood-2013-11-540526

Journal Article Type Article
Acceptance Date Feb 26, 2014
Online Publication Date Mar 18, 2014
Publication Date May 15, 2014
Deposit Date Apr 9, 2019
Publicly Available Date Mar 12, 2021
Journal Blood
Print ISSN 0006-4971
Electronic ISSN 1528-0020
Publisher American Society of Hematology
Peer Reviewed Peer Reviewed
Volume 123
Issue 20
Pages 3166-3174
DOI https://doi.org/10.1182/blood-2013-11-540526
Keywords Bacteria; Blood platelets; Platelet activation; Platelet factor 4; Platelet aggregation; Granules; Immunoglobulin g; Integrins; Tyrosine; Staphylococcus aureus
Public URL https://hull-repository.worktribe.com/output/1563115
Publisher URL http://www.bloodjournal.org/content/123/20/3166

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Copyright Statement
© 2014 by The American Society of Hematology



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