Intramuscular Exposure to a Lethal Dose of Ricin Toxin Leads to Endothelial Glycocalyx Shedding and Microvascular Flow Abnormality in Mice and Swine

Ricin toxin isolated from the castor bean (<i>Ricinus communis</i>) is one of the most potent and lethal molecules known. While the pathophysiology and clinical consequences of ricin poisoning by the parenteral route, i.e., intramuscular penetration, have been described recently in vario...

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Autores principales:	Anita Sapoznikov, Yoav Gal, Yentl Evgy, Moshe Aftalion, Shahaf Katalan, Tamar Sabo, Chanoch Kronman, Reut Falach
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	ricin intramuscular glycocalyx shedding heparan sulfate hyaluronic acid syndecan-1 Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/0b91a9f1acf747ff990e8c9006b2be9d
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spelling	oai:doaj.org-article:0b91a9f1acf747ff990e8c9006b2be9d2021-11-25T17:55:35ZIntramuscular Exposure to a Lethal Dose of Ricin Toxin Leads to Endothelial Glycocalyx Shedding and Microvascular Flow Abnormality in Mice and Swine10.3390/ijms2222123451422-00671661-6596https://doaj.org/article/0b91a9f1acf747ff990e8c9006b2be9d2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12345https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Ricin toxin isolated from the castor bean (<i>Ricinus communis</i>) is one of the most potent and lethal molecules known. While the pathophysiology and clinical consequences of ricin poisoning by the parenteral route, i.e., intramuscular penetration, have been described recently in various animal models, the preceding mechanism underlying the clinical manifestations of systemic ricin poisoning has not been completely defined. Here, we show that following intramuscular administration, ricin bound preferentially to the vasculature in both mice and swine, leading to coagulopathy and widespread hemorrhages. Increased levels of circulating VEGF and decreased expression of vascular VE-cadherin caused blood vessel impairment, thereby promoting hyperpermeability in various organs. Elevated levels of soluble heparan sulfate, hyaluronic acid and syndecan-1 were measured in blood samples following ricin intoxication, indicating that the vascular glycocalyx of both mice and swine underwent extensive damage. Finally, by using side-stream dark field intravital microscopy imaging, we determined that ricin poisoning leads to microvasculature malfunctioning, as manifested by aberrant blood flow and a significant decrease in the number of diffused microvessels. These findings, which suggest that glycocalyx shedding and microcirculation dysfunction play a major role in the pathology of systemic ricin poisoning, may serve for the formulation of specifically tailored therapies for treating parenteral ricin intoxication.Anita SapoznikovYoav GalYentl EvgyMoshe AftalionShahaf KatalanTamar SaboChanoch KronmanReut FalachMDPI AGarticlericinintramuscularglycocalyx sheddingheparan sulfatehyaluronic acidsyndecan-1Biology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12345, p 12345 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ricin intramuscular glycocalyx shedding heparan sulfate hyaluronic acid syndecan-1 Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	ricin intramuscular glycocalyx shedding heparan sulfate hyaluronic acid syndecan-1 Biology (General) QH301-705.5 Chemistry QD1-999 Anita Sapoznikov Yoav Gal Yentl Evgy Moshe Aftalion Shahaf Katalan Tamar Sabo Chanoch Kronman Reut Falach Intramuscular Exposure to a Lethal Dose of Ricin Toxin Leads to Endothelial Glycocalyx Shedding and Microvascular Flow Abnormality in Mice and Swine
description	Ricin toxin isolated from the castor bean (<i>Ricinus communis</i>) is one of the most potent and lethal molecules known. While the pathophysiology and clinical consequences of ricin poisoning by the parenteral route, i.e., intramuscular penetration, have been described recently in various animal models, the preceding mechanism underlying the clinical manifestations of systemic ricin poisoning has not been completely defined. Here, we show that following intramuscular administration, ricin bound preferentially to the vasculature in both mice and swine, leading to coagulopathy and widespread hemorrhages. Increased levels of circulating VEGF and decreased expression of vascular VE-cadherin caused blood vessel impairment, thereby promoting hyperpermeability in various organs. Elevated levels of soluble heparan sulfate, hyaluronic acid and syndecan-1 were measured in blood samples following ricin intoxication, indicating that the vascular glycocalyx of both mice and swine underwent extensive damage. Finally, by using side-stream dark field intravital microscopy imaging, we determined that ricin poisoning leads to microvasculature malfunctioning, as manifested by aberrant blood flow and a significant decrease in the number of diffused microvessels. These findings, which suggest that glycocalyx shedding and microcirculation dysfunction play a major role in the pathology of systemic ricin poisoning, may serve for the formulation of specifically tailored therapies for treating parenteral ricin intoxication.
format	article
author	Anita Sapoznikov Yoav Gal Yentl Evgy Moshe Aftalion Shahaf Katalan Tamar Sabo Chanoch Kronman Reut Falach
author_facet	Anita Sapoznikov Yoav Gal Yentl Evgy Moshe Aftalion Shahaf Katalan Tamar Sabo Chanoch Kronman Reut Falach
author_sort	Anita Sapoznikov
title	Intramuscular Exposure to a Lethal Dose of Ricin Toxin Leads to Endothelial Glycocalyx Shedding and Microvascular Flow Abnormality in Mice and Swine
title_short	Intramuscular Exposure to a Lethal Dose of Ricin Toxin Leads to Endothelial Glycocalyx Shedding and Microvascular Flow Abnormality in Mice and Swine
title_full	Intramuscular Exposure to a Lethal Dose of Ricin Toxin Leads to Endothelial Glycocalyx Shedding and Microvascular Flow Abnormality in Mice and Swine
title_fullStr	Intramuscular Exposure to a Lethal Dose of Ricin Toxin Leads to Endothelial Glycocalyx Shedding and Microvascular Flow Abnormality in Mice and Swine
title_full_unstemmed	Intramuscular Exposure to a Lethal Dose of Ricin Toxin Leads to Endothelial Glycocalyx Shedding and Microvascular Flow Abnormality in Mice and Swine
title_sort	intramuscular exposure to a lethal dose of ricin toxin leads to endothelial glycocalyx shedding and microvascular flow abnormality in mice and swine
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/0b91a9f1acf747ff990e8c9006b2be9d
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Intramuscular Exposure to a Lethal Dose of Ricin Toxin Leads to Endothelial Glycocalyx Shedding and Microvascular Flow Abnormality in Mice and Swine

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