Immunohistochemical detection of the vomiting-inducing monoamine neurotransmitter serotonin and enterochromaffin cells in the intestines of conventional or gnotobiotic (Gn) pigs infected with porcine epidemic diarrhea virus (PEDV) and serum cytokine responses of Gn pigs to acute PEDV infection.

Immunohistochemical detection of the vomiting-inducing monoamine neurotransmitter serotonin and enterochromaffin cells in the intestines of conventional or gnotobiotic (Gn) pigs infected with porcine epidemic diarrhea virus (PEDV) and serum cytokine responses of Gn pigs to acute PEDV infection.
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DOI:
10.1016/j.rvsc.2018.06.009
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发表时间:
2018-08
影响因子:
2.4
通讯作者:
Saif LJ
Saif LJ
中科院分区:
农林科学3区
文献类型:
--
作者:
Jung K;Miyazaki A;Saif LJ

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5-羟色胺是一种重要的单胺类神经递质分子,由肠嗜铬细胞(EC)储存和释放到肠粘膜下层,将呕吐信号传递到大脑。通过免疫组织化学方法对猪EC细胞进行鉴定,研究了猪流行性腹泻病毒(PEDV)感染后引起呕吐的一种机制。用PEDV PC 21 A菌株或模拟物经口(8.9-9.2 log 10基因组当量/猪)接种常规或无菌(Gn)9日龄猪[PEDV接种(n = 12);模拟物(n = 14)]。这是第一次通过免疫组织化学方法在猪中鉴定出降钙素阳性EC细胞,并且主要在肠隐窝中,无论感染状态如何。它们在形态上分别为三角形或圆形细胞,有或没有顶端细胞质延伸。在接种后16或24小时,当呕吐是第一次或经常观察到,分别,PEDV感染导致显着减少的十二指肠,空肠中段,回肠,或结肠中的大肠杆菌阳性EC细胞的数量。然而,在PIH 16时尚未显示呕吐的三只PEDV接种Gn猪中的两只在十二指肠、回肠和结肠中具有与阴性对照中相似的马克隆宁阳性EC细胞的数量。这些发现表明,5-羟色胺从EC细胞释放(增加的5-羟色胺水平)到肠粘膜下层中可能在PEDV感染后早期发生,以刺激迷走传入神经元,随后呕吐。5-羟色胺可能参与了PEDV感染仔猪呕吐的相关机制。我们还发现,空肠中段是急性PEDV感染的主要部位,并且在PEDV感染的急性阶段诱导全身性先天性和促炎性细胞因子应答。5-羟色胺是由肠嗜铬细胞分泌的呕吐相关神经递质。急性PEDV感染显著导致小肠和大肠中的大肠杆菌素阳性EC细胞数量减少。PEDV感染诱导全身先天性和促炎性细胞因子反应的gnotobiotic猪。5-羟色胺可能参与了PEDV感染仔猪呕吐的相关机制。
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 log10 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. Serotonin is the vomiting-related neurotransmitter secreted from enterochromaffin (EC) cells. Acute PEDV infection significantly resulted in reduced numbers of serotonin-positive EC cells in the small and large intestines. PEDV infection induced systemic innate and pro-inflammatory cytokine responses in gnotobiotic pigs. Serotonin might be involved in the mechanisms related to vomiting in PEDV-infected nursing pigs.
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