4.6 Article

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

期刊

JOURNAL OF THROMBOSIS AND HAEMOSTASIS
卷 11, 期 5, 页码 941-950

出版社

WILEY-BLACKWELL
DOI: 10.1111/jth.12175

关键词

FcgammaRIIA; GPIb; infective endocarditis; platelets; Streptococcus oralis

资金

  1. Irish Research Council for Science, Engineering and Technology
  2. British Heart Foundation
  3. Science Foundation of Ireland
  4. British Heart Foundation [PG/13/42/30309, PG/10/88/28628] Funding Source: researchfish

向作者/读者索取更多资源

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 (50200s1) and arterial shear conditions (800s1). Platelets rolled along immobilized S.oralis through an interaction with GPIb. 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 FcRIIa. This interaction led to phosphorylation of the ITAM domain on FcRIIa, 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.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据