Glycoprotein Ibα and FcγRIIa play key roles in platelet activation by the colonizing bacterium, Streptococcus oralis

Tilley, D. O.; Arman, M.; Smolenski, A.; Cox, D.; O'Donnell, J. S.; Douglas, C. W.I.; Watson, S. P.; Kerrigan, S. W.

Abstract

Background: Infective endocarditis (IE) is characterized by thrombus formation on a cardiac valve. The oral bacterium, Streptococcus oralis, is recognized for its ability to colonize damaged heart valves and is frequently isolated from patients with IE. Platelet interaction with S. oralis leads to the development of a thrombotic vegetation on heart valves, which results in valvular incompetence and congestive heart failure. Objective: To investigate the mechanism through which platelets become activated upon binding S. oralis. Patients and Methods: Platelet interactions with immobilized bacteria under shear conditions were assessed using a parallel flow chamber. S. oralis-inducible platelet reactivity was determined using light transmission aggregometry. Dense granule secretion was measured by luminometry using a luciferin/luciferase assay. Results: Using shear rates that mimic physiological conditions, we demonstrated that S. oralis was able to support platelet adhesion under venous (50-200 s-1) and arterial shear conditions (800 s-1). Platelets rolled along immobilized S. oralis through an interaction with GPIbα. Following rolling, platelet microaggregate formation was observed on immobilized S. oralis. Aggregate formation was dependent on S. oralis binding IgG, which cross-links to platelet FcγRIIa. This interaction led to phosphorylation of the ITAM domain on FcγRIIa, resulting in dense granule secretion, amplification through the ADP receptor and activation of RAP1, culminating in platelet microaggregate formation. Conclusions: These results suggest a model of interaction between S. oralis and platelets that leads to the formation of a stable septic vegetation on damaged heart valves. © 2013 International Society on Thrombosis and Haemostasis.

Citation

Tilley, D. O., Arman, M., Smolenski, A., Cox, D., O'Donnell, J. S., Douglas, C. W., …Kerrigan, S. W. (2013). Glycoprotein Ibα and FcγRIIa play key roles in platelet activation by the colonizing bacterium, Streptococcus oralis. Journal of thrombosis and haemostasis : JTH, 11(5), 941-950. https://doi.org/10.1111/jth.12175

• Journal Article Type: Article
• Acceptance Date: Feb 11, 2013
• Online Publication Date: Feb 16, 2013
• Publication Date: 2013-05
• Deposit Date: May 5, 2022
• Journal: Journal of Thrombosis and Haemostasis
• Print ISSN: 1538-7933
• Electronic ISSN: 1538-7836
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Issue: 5
• Pages: 941-950
• DOI: https://doi.org/10.1111/jth.12175
• Keywords: FcgammaRIIA; GPIb; Infective endocarditis; Platelets; Streptococcus oralis
• Public URL: https://hull-repository.worktribe.com/output/3571141