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.

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