心内膜炎病原体通过激活的血小板诱导血管内中性粒细胞细胞外陷阱促进赘生物形成。
Endocarditis pathogen promotes vegetation formation by inducing intravascular neutrophil extracellular traps through activated platelets.
机构信息
From the Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan (C.-J.J., J.-S.C.); Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan (C.-Y.Y., J.-S.C.); Department of Surgery, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan (R.-B.H.); Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan (C.-M.L.); and Department of Forensic Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan (C.-T.S.).
出版信息
Circulation. 2015 Feb 10;131(6):571-81. doi: 10.1161/CIRCULATIONAHA.114.011432. Epub 2014 Dec 19.
BACKGROUND
Endocarditis-inducing streptococci form multilayered biofilms in complex with aggregated platelets on injured heart valves, but the host factors that interconnect and entrap these bacteria-platelet aggregates to promote vegetation formation were unclear.
METHODS AND RESULTS
In a Streptococcus mutans endocarditis rat model, we identified layers of neutrophil extracellular traps interconnecting and entrapping bacteria-platelet aggregates inside vegetation that could be reduced significantly in size along with diminished colonizing bacteria by prophylaxis with intravascular DNase I alone. The combination of activated platelets and specific immunoglobulin G-adsorbed bacteria are required to induce the formation of neutrophil extracellular traps through multiple activation pathways. Bacteria play key roles in coordinating the signaling through spleen tyrosine kinase, Src family kinases, phosphatidylinositol-3-kinase, and p38 mitogen-activated protein kinase pathways to upregulate the expression of P-selectin in platelets, while inducing reactive oxygen species-dependent citrullination in the arm of neutrophils. Neutrophil extracellular traps in turn serve as the scaffold to further enhance and entrap bacteria-platelet aggregate formation and expansion.
CONCLUSIONS
Neutrophil extracellular traps promote and expand vegetation formation through enhancing and entrapping bacteria-platelet aggregates on the injured heart valves.
背景
感染性心内膜炎的链球菌在受伤的心脏瓣膜上与聚集的血小板形成多层生物膜，但连接和捕获这些细菌-血小板聚集体以促进赘生物形成的宿主因素尚不清楚。
方法和结果
在变形链球菌心内膜炎大鼠模型中，我们发现中性粒细胞细胞外诱捕网的层相互连接并捕获了在赘生物中的细菌-血小板聚集体，通过单独使用血管内 DNA 酶 I 进行预防，可以显著减小其大小并减少定植细菌。激活的血小板和特异性免疫球蛋白 G 吸附的细菌通过多种激活途径共同诱导中性粒细胞细胞外诱捕网的形成。细菌在协调信号转导中起关键作用，通过脾酪氨酸激酶、Src 家族激酶、磷酸肌醇-3-激酶和 p38 丝裂原活化蛋白激酶途径上调血小板中 P-选择素的表达，同时诱导中性粒细胞的依赖活性氧物质的瓜氨酸化。中性粒细胞细胞外诱捕网反过来又作为支架，进一步增强和捕获细菌-血小板聚集体的形成和扩张。
结论
中性粒细胞细胞外诱捕网通过增强和捕获受伤心脏瓣膜上的细菌-血小板聚集体来促进和扩大赘生物的形成。
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