The Mechanism of Pertussis Cough Revealed by the Mouse-Coughing Model.
The Mechanism of Pertussis Cough Revealed by the Mouse-Coughing Model.
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百日咳，也被称为百日咳，是一种由革兰氏阴性细菌百日咳博德泰拉引起的传染性呼吸道疾病。这种疾病的特点是严重和无法控制的咳嗽，这给患者带来了沉重的负担。然而，由于缺乏复制咳嗽的通用动物模型，其病因和机制完全未知。在这里，我们建立了一个小鼠模型，在鼻内接种细菌或其成分后复制咳嗽，并证明细菌的低脂寡糖（LOS），百日咳毒素（PTx）和Vag8协同作用引起咳嗽。由LOS诱导的缓激肽使瞬时受体电位离子通道TRPV1增敏，TRPV1作为传感器引起咳嗽反射。Vag8通过抑制C1酯酶抑制剂进一步增加缓激肽水平，C1酯酶抑制剂是产生缓激肽的接触系统的主要下调因子。PTx通过Gi gtpase的失活抑制TRPV1的内在负调控系统。我们的研究结果为回答百日咳的病理生理长期存在的问题提供了基础。
Pertussis, also known as whooping cough, is a contagious respiratory disease caused by the Gram-negative bacterium Bordetella pertussis. This disease is characterized by severe and uncontrollable coughing, which imposes a significant burden on patients. However, its etiological agent and the mechanism are totally unknown because of a lack of versatile animal models that reproduce the cough. Here, we present a mouse model that reproduces coughing after intranasal inoculation with the bacterium or its components and demonstrate that lipooligosaccharide (LOS), pertussis toxin (PTx), and Vag8 of the bacterium cooperatively function to cause coughing. Bradykinin induced by LOS sensitized a transient receptor potential ion channel, TRPV1, which acts as a sensor to evoke the cough reflex. Vag8 further increased bradykinin levels by inhibiting the C1 esterase inhibitor, the major downregulator of the contact system, which generates bradykinin. PTx inhibits intrinsic negative regulation systems for TRPV1 through the inactivation of Gi GTPases. Our findings provide a basis to answer long-standing questions on the pathophysiology of pertussis cough.
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DOI：
10.1124/jpet.102.043422
发表时间：
2003-03-01
影响因子：
3.5
作者：
Carr, MJ;Kollarik, M;Undem, BJ
通讯作者：
Undem, BJ
影响因子：
3.1
作者：
Hall, E;Parton, R;Wardlaw, AC
通讯作者：
Wardlaw, AC
影响因子：
4.2
作者：
Buasri, Wasin;Impoolsup, Attawut;Panbangred, Watanalai
通讯作者：
Panbangred, Watanalai
影响因子：
3.2
作者：
Bonvini, Sara J.;Belvisi, Maria G.
通讯作者：
Belvisi, Maria G.
影响因子：
3.1
作者：
Diehl, Sean A.;McElvany, Benjamin;Teuscher, Cory
通讯作者：
Teuscher, Cory