Histamine release from intestinal mast cells induced by staphylococcal enterotoxin A (SEA) evokes vomiting reflex in common marmoset
Histamine release from intestinal mast cells induced by staphylococcal enterotoxin A (SEA) evokes vomiting reflex in common marmoset
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DOI：
10.1371/journal.ppat.1007803
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发表时间：
2019-05-01
期刊：
影响因子：
6.7
通讯作者：
Nakane, Akio
中科院分区：
文献类型：
--
作者：
Ono, Hisaya K.;Hirose, Shouhei;Nakane, Akio
由金黄色葡萄球菌产生的葡萄球菌肠毒素是引起呕吐性食物中毒的主要原因。我们以前证明，SEA结合粘膜下肥大细胞，并引起肥大细胞脱粒在一个小的呕吐的家麝鼩模型。值得注意的是，灵长类动物已被公认为用于呕吐测定和SE呕吐活性分析的标准模型。然而，SEA诱导灵长类动物呕吐的机制尚未阐明。本研究建立了普通绒猴呕吐动物模型。普通绒猴给予经典SE，包括SEA、SEB和SEC，并表现出多次呕吐反应。然而，非呕吐性葡萄球菌超抗原，中毒性休克综合征毒素-1，并没有引起这些猴子呕吐。这些结果表明，普通绒猴是一个有用的动物模型，用于评估呕吐的SEs的诱导活性。此外，组织学分析发现SEA与粘膜下肥大细胞结合并诱导肥大细胞脱颗粒。此外，离体和体内药理学结果表明，SEA诱导的组胺释放在普通绒猴的呕吐反应中起着关键作用。结果提示，5-羟色胺在迷走传入神经或中枢神经系统传递催吐刺激中也起重要作用。我们的结论是，SEA诱导组胺释放粘膜下肥大细胞在胃肠道和组胺有助于SEA引起的呕吐反射通过交感神经和/或其他迷走神经。
Staphylococcal enterotoxins (SEs) produced by Staphylococcus aureus are known as causative agents of emetic food poisoning. We previously demonstrated that SEA binds with submucosal mast cells and evokes mast cell degranulation in a small emetic house musk shrew model. Notably, primates have been recognized as the standard model for emetic assays and analysis of SE emetic activity. However, the mechanism involved in SEA-induced vomiting in primates has not yet been elucidated. In the present study, we established common marmosets as an emetic animal model. Common marmosets were administered classical SEs, including SEA, SEB and SEC, and exhibited multiple vomiting responses. However, a non-emetic staphylococcal superantigen, toxic shock syndrome toxin-1, did not induce emesis in these monkeys. These results indicated that the common marmoset is a useful animal model for assessing the emesis-inducing activity of SEs. Furthermore, histological analysis uncovered that SEA bound with submucosal mast cells and induced mast cell degranulation. Additionally, ex vivo and in vivo pharmacological results showed that SEA-induced histamine release plays a critical role in the vomiting response in common marmosets. The present results suggested that 5-hydroxytryptamine also plays an important role in the transmission of emetic stimulation on the afferent vagus nerve or central nervous system. We conclude that SEA induces histamine release from submucosal mast cells in the gastrointestinal tract and that histamine contributes to the SEA-induced vomiting reflex via the serotonergic nerve and/or other vagus nerve.