G Proteins Gαi1/3 Are Critical Targets for Bordetella pertussis Toxin-Induced Vasoactive Amine Sensitization
G Proteins Gαi1/3 Are Critical Targets for Bordetella pertussis Toxin-Induced Vasoactive Amine Sensitization
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DOI：
10.1128/iai.00971-13
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发表时间：
2014-02-01
影响因子：
3.1
通讯作者：
Teuscher, Cory
中科院分区：
文献类型：
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作者：
Diehl, Sean A.;McElvany, Benjamin;Teuscher, Cory
百日咳毒素（PTX）是由百日咳杆菌（Bordetella pertussis）产生的AB 5型外毒素，百日咳的病原体。体内PTX中毒可引起多种免疫和炎症反应，包括对组胺（HA）、5-羟色胺（5-HT）和缓激肽（BDK）的血管活性胺敏化（VAAS）。以前，通过使用正向遗传学方法，我们确定了HA H-1受体（Hrh 1/H1 R）作为小鼠中控制对B的不同易感性的基因。百日咳PTX诱导的HA致敏（Bphs）。在这里，我们表明，通过使用近交系小鼠，F-1杂交，和分离的人口，即，不像Bphs，PTX诱导的5-HT敏感性（Bpss）和BDK敏感性（Bpbs）是隐性性状，分别由多个位点不连锁的5-HT和BDK受体，分别控制。此外，我们发现，PTX致敏小鼠HA独立的Toll样受体4，一个假定的PTX受体，和PTX的VAAS特性不依赖于内皮细胞小窝或内皮细胞一氧化氮合酶。最后，通过使用单个G α（i/o）G蛋白亚基缺陷的小鼠，我们证明G α（i1）和G α（i3）是PTX暴露引起VAAS的ADP核糖基化的关键体内靶点。
Pertussis toxin (PTX) is an AB5-type exotoxin produced by the bacterium Bordetella pertussis, the causative agent of whooping cough. In vivo intoxication with PTX elicits a variety of immunologic and inflammatory responses, including vasoactive amine sensitization (VAAS) to histamine (HA), serotonin (5-HT), and bradykinin (BDK). Previously, by using a forward genetic approach, we identified the HA H-1 receptor (Hrh1/ H1R) as the gene in mice that controls differential susceptibility to B. pertussis PTX-induced HA sensitization (Bphs). Here we show, by using inbred strains of mice, F-1 hybrids, and segregating populations, that, unlike Bphs, PTX-induced 5-HT sensitivity (Bpss) and BDK sensitivity (Bpbs) are recessive traits and are separately controlled by multiple loci unlinked to 5-HT and BDK receptors, respectively. Furthermore, we found that PTX sensitizes mice to HA independently of Toll-like receptor 4, a purported receptor for PTX, and that the VAAS properties of PTX are not dependent upon endothelial caveolae or endothelial nitric oxide synthase. Finally, by using mice deficient in individual G alpha(i/o) G-protein subunits, we demonstrate that G alpha(i1) and G alpha(i3) are the critical in vivo targets of ADP-ribosylation underlying VAAS elicited by PTX exposure.