Jung Kwonil, Miyazaki Ayako, Saif Linda J
Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster, OH, USA.
Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster, OH, USA; Division of Virology and Epidemiology, National Institute of Animal Health, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan.
Res Vet Sci. 2018 Aug;119:99-108. doi: 10.1016/j.rvsc.2018.06.009. Epub 2018 Jun 12.
Serotonin is a critical monoamine neurotransmitter molecule stored and released from enterochromaffin (EC) cells into the gut submucosa, transmitting the vomiting signal to the brain. We studied one mechanism by which vomiting is induced in pigs infected with porcine epidemic diarrhea virus (PEDV) by characterization of swine EC cells by immunohistochemistry. Conventional or gnotobiotic (Gn) 9-day-old pigs [PEDV-inoculated (n = 12); Mock (n = 14)] were inoculated orally (8.9-9.2 log genomic equivalents/pig) with PEDV PC21A strain or mock. This is the first identification of serotonin-positive EC cells in swine by immunohistochemistry and mainly in intestinal crypts, regardless of infection status. They were morphologically triangular-shaped or round cells with or without apical cytoplasmic extensions, respectively. At post-inoculation hour (PIH) 16 or 24, when vomiting was first or frequently observed, respectively, PEDV infection resulted in significantly reduced numbers of serotonin-positive EC cells in duodenum, mid-jejunum, ileum, or colon. However, two of three PEDV-inoculated Gn pigs that did not yet show vomiting at PIH 16 had numbers of serotonin-positive EC cells in duodenum, ileum and colon similar to those in the negative controls. These findings suggest that serotonin release from EC cells (increased serotonin levels) into the gut submucosa might occur early PEDV post-infection to stimulate the vagal afferent neurons, followed by vomiting. Serotonin might be involved in the mechanisms related to vomiting in PEDV-infected piglets. We also found that mid-jejunum was the primary site of acute PEDV infection, and that systemic innate and pro-inflammatory cytokine responses were induced during the acute stage of PEDV infection.
血清素是一种关键的单胺神经递质分子，由肠嗜铬（EC）细胞储存并释放到肠道黏膜下层，将呕吐信号传递至大脑。我们通过免疫组织化学对猪EC细胞进行表征，研究了感染猪流行性腹泻病毒（PEDV）的猪诱发呕吐的一种机制。将常规或无菌（Gn）9日龄仔猪[接种PEDV（n = 12）；假接种（n = 14）]经口接种（8.9 - 9.2 log基因组当量/头）PEDV PC21A毒株或进行假接种。这是首次通过免疫组织化学在猪中鉴定出血清素阳性EC细胞，且主要存在于肠隐窝中，与感染状态无关。它们在形态上分别为三角形或圆形细胞，有无顶端细胞质延伸。在接种后16小时（PIH）或24小时，分别是首次观察到呕吐或频繁观察到呕吐时，PEDV感染导致十二指肠、空肠中段、回肠或结肠中血清素阳性EC细胞数量显著减少。然而，在PIH 16时未出现呕吐的三只接种PEDV的Gn猪中，有两只猪十二指肠、回肠和结肠中的血清素阳性EC细胞数量与阴性对照相似。这些发现表明，PEDV感染后早期，EC细胞向肠道黏膜下层释放血清素（血清素水平升高）可能会刺激迷走神经传入神经元，随后引发呕吐。血清素可能参与了PEDV感染仔猪呕吐相关的机制。我们还发现空肠中段是PEDV急性感染的主要部位，并且在PEDV感染的急性期会诱导全身性固有和促炎细胞因子反应。
