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Diverse Profiles of Ricin-Cell Interactions in the Lung Following Intranasal Exposure to Ricin

Ricin, a plant-derived exotoxin, inhibits protein synthesis by ribosomal inactivation. Due to its wide availability and ease of preparation, ricin is considered a biothreat, foremost by respiratory exposure. We examined the in vivo interactions between ricin and cells of the lungs in mice intranasal...

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Autores principales: Sapoznikov, Anita, Falach, Reut, Mazor, Ohad, Alcalay, Ron, Gal, Yoav, Seliger, Nehama, Sabo, Tamar, Kronman, Chanoch
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4663535/
https://www.ncbi.nlm.nih.gov/pubmed/26593946
http://dx.doi.org/10.3390/toxins7114817
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author Sapoznikov, Anita
Falach, Reut
Mazor, Ohad
Alcalay, Ron
Gal, Yoav
Seliger, Nehama
Sabo, Tamar
Kronman, Chanoch
author_facet Sapoznikov, Anita
Falach, Reut
Mazor, Ohad
Alcalay, Ron
Gal, Yoav
Seliger, Nehama
Sabo, Tamar
Kronman, Chanoch
author_sort Sapoznikov, Anita
collection PubMed
description Ricin, a plant-derived exotoxin, inhibits protein synthesis by ribosomal inactivation. Due to its wide availability and ease of preparation, ricin is considered a biothreat, foremost by respiratory exposure. We examined the in vivo interactions between ricin and cells of the lungs in mice intranasally exposed to the toxin and revealed multi-phasic cell-type-dependent binding profiles. While macrophages (MΦs) and dendritic cells (DCs) displayed biphasic binding to ricin, monophasic binding patterns were observed for other cell types; epithelial cells displayed early binding, while B cells and endothelial cells bound toxin late after intoxication. Neutrophils, which were massively recruited to the intoxicated lung, were refractive to toxin binding. Although epithelial cells bound ricin as early as MΦs and DCs, their rates of elimination differed considerably; a reduction in epithelial cell counts occurred late after intoxication and was restricted to alveolar type II cells only. The differential binding and cell-elimination patterns observed may stem from dissimilar accessibility of the toxin to different cells in the lung and may also reflect unequal interactions of the toxin with different cell-surface receptors. The multifaceted interactions observed in this study between ricin and the various cells of the target organ should be considered in the future development of efficient post-exposure countermeasures against ricin intoxication.
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spelling pubmed-46635352015-12-10 Diverse Profiles of Ricin-Cell Interactions in the Lung Following Intranasal Exposure to Ricin Sapoznikov, Anita Falach, Reut Mazor, Ohad Alcalay, Ron Gal, Yoav Seliger, Nehama Sabo, Tamar Kronman, Chanoch Toxins (Basel) Article Ricin, a plant-derived exotoxin, inhibits protein synthesis by ribosomal inactivation. Due to its wide availability and ease of preparation, ricin is considered a biothreat, foremost by respiratory exposure. We examined the in vivo interactions between ricin and cells of the lungs in mice intranasally exposed to the toxin and revealed multi-phasic cell-type-dependent binding profiles. While macrophages (MΦs) and dendritic cells (DCs) displayed biphasic binding to ricin, monophasic binding patterns were observed for other cell types; epithelial cells displayed early binding, while B cells and endothelial cells bound toxin late after intoxication. Neutrophils, which were massively recruited to the intoxicated lung, were refractive to toxin binding. Although epithelial cells bound ricin as early as MΦs and DCs, their rates of elimination differed considerably; a reduction in epithelial cell counts occurred late after intoxication and was restricted to alveolar type II cells only. The differential binding and cell-elimination patterns observed may stem from dissimilar accessibility of the toxin to different cells in the lung and may also reflect unequal interactions of the toxin with different cell-surface receptors. The multifaceted interactions observed in this study between ricin and the various cells of the target organ should be considered in the future development of efficient post-exposure countermeasures against ricin intoxication. MDPI 2015-11-17 /pmc/articles/PMC4663535/ /pubmed/26593946 http://dx.doi.org/10.3390/toxins7114817 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sapoznikov, Anita
Falach, Reut
Mazor, Ohad
Alcalay, Ron
Gal, Yoav
Seliger, Nehama
Sabo, Tamar
Kronman, Chanoch
Diverse Profiles of Ricin-Cell Interactions in the Lung Following Intranasal Exposure to Ricin
title Diverse Profiles of Ricin-Cell Interactions in the Lung Following Intranasal Exposure to Ricin
title_full Diverse Profiles of Ricin-Cell Interactions in the Lung Following Intranasal Exposure to Ricin
title_fullStr Diverse Profiles of Ricin-Cell Interactions in the Lung Following Intranasal Exposure to Ricin
title_full_unstemmed Diverse Profiles of Ricin-Cell Interactions in the Lung Following Intranasal Exposure to Ricin
title_short Diverse Profiles of Ricin-Cell Interactions in the Lung Following Intranasal Exposure to Ricin
title_sort diverse profiles of ricin-cell interactions in the lung following intranasal exposure to ricin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4663535/
https://www.ncbi.nlm.nih.gov/pubmed/26593946
http://dx.doi.org/10.3390/toxins7114817
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