Document Detail


Glycoprotein Ibα and FcγRIIa play key roles in platelet activation by the colonizing bacterium, Streptococcus oralis.
MedLine Citation:
PMID:  23413961     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
D O Tilley; M Arman; A Smolenski; D Cox; J S O'Donnell; C W I Douglas; S P Watson; S W Kerrigan
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of thrombosis and haemostasis : JTH     Volume:  11     ISSN:  1538-7836     ISO Abbreviation:  J. Thromb. Haemost.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-05-16     Completed Date:  2014-01-03     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  101170508     Medline TA:  J Thromb Haemost     Country:  England    
Other Details:
Languages:  eng     Pagination:  941-50     Citation Subset:  IM    
Copyright Information:
© 2013 International Society on Thrombosis and Haemostasis.
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MeSH Terms
Descriptor/Qualifier:
Cell Adhesion
Endocarditis / blood,  microbiology
Humans
Platelet Activation / physiology*
Platelet Aggregation
Platelet Glycoprotein GPIb-IX Complex / physiology*
Receptors, IgG / physiology*
Streptococcus oralis / physiology*
Grant Support
ID/Acronym/Agency:
PG/10/88/28628//British Heart Foundation
Chemical
Reg. No./Substance:
0/Fc gamma receptor IIA; 0/Platelet Glycoprotein GPIb-IX Complex; 0/Receptors, IgG

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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