Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
PLoS One. 2013 Jul 17;8(7):e69706. doi: 10.1371/journal.pone.0069706. Print 2013.
Ricin is a potent toxin found in the beans of Ricinus communis and is often lethal for animals and humans when aerosolized or injected and causes significant morbidity and occasional death when ingested. Ricin has been proposed as a bioweapon because of its lethal properties, environmental stability, and accessibility. In oral intoxication, the process by which the toxin transits across intestinal mucosa is not completely understood. To address this question, we assessed the impact of ricin on the gastrointestinal tract and organs of mice after dissemination of toxin from the gut. We first showed that ricin adhered in a specific pattern to human small bowel intestinal sections, the site within the mouse gut in which a variable degree of damage has been reported by others. We then monitored the movement of ricin across polarized human HCT-8 intestinal monolayers grown in transwell inserts and in HCT-8 cell organoids. We observed that, in both systems, ricin trafficked through the cells without apparent damage until 24 hours post intoxication. We delivered a lethal dose of purified fluorescently-labeled ricin to mice by oral gavage and followed transit of the toxin from the gastrointestinal tracts to the internal organs by in vivo imaging of whole animals over time and ex vivo imaging of organs at various time points. In addition, we harvested organs from unlabeled ricin-gavaged mice and assessed them for the presence of ricin and for histological damage. Finally, we compared serum chemistry values from buffer-treated versus ricin-intoxicated animals. We conclude that ricin transverses human intestinal cells and mouse intestinal cells in situ prior to any indication of enterocyte damage and that ricin rapidly reaches the kidneys of intoxicated mice. We also propose that mice intoxicated orally with ricin likely die from distributive shock.
蓖麻毒素是一种存在于蓖麻（Ricinus communis）豆中的有效毒素，当雾化或注射时，对动物和人类往往是致命的，而当摄入时，则会导致严重的发病率和偶尔的死亡。由于其致命特性、环境稳定性和可获得性，蓖麻毒素已被提议作为一种生物武器。在口服中毒的情况下，毒素穿过肠黏膜的过程尚未完全了解。为了解决这个问题，我们评估了毒素从肠道传播后对小鼠胃肠道和器官的影响。我们首先表明，蓖麻毒素以特定的模式附着在人类小肠肠段上，这是其他研究报道的在小鼠肠道中存在一定程度损伤的部位。然后，我们监测了在 Transwell 插入物中生长的极化人 HCT-8 肠单层和 HCT-8 细胞类器官中蓖麻毒素穿过的情况。我们观察到，在这两种系统中，蓖麻毒素在没有明显损伤的情况下穿过细胞，直到中毒后 24 小时。我们通过口服灌胃向小鼠提供了致死剂量的纯化荧光标记的蓖麻毒素，并通过对整个动物进行体内成像，以及在不同时间点对器官进行离体成像，来跟踪从胃肠道到内部器官的毒素转移情况。此外，我们从未标记的蓖麻毒素灌胃的小鼠中采集器官，并评估其是否存在蓖麻毒素以及组织学损伤。最后，我们比较了缓冲液处理的动物和蓖麻毒素中毒的动物的血清化学值。我们得出的结论是，蓖麻毒素在肠细胞出现任何损伤迹象之前穿过人肠细胞和鼠肠细胞，并且蓖麻毒素迅速到达中毒小鼠的肾脏。我们还提出，口服蓖麻毒素中毒的小鼠可能死于分布性休克。
