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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MDPI AG
2015-11-01
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Online Access: | http://www.mdpi.com/2072-6651/7/11/4817 |
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author | Anita Sapoznikov Reut Falach Ohad Mazor Ron Alcalay Yoav Gal Nehama Seliger Tamar Sabo Chanoch Kronman |
author_facet | Anita Sapoznikov Reut Falach Ohad Mazor Ron Alcalay Yoav Gal Nehama Seliger Tamar Sabo Chanoch Kronman |
author_sort | Anita Sapoznikov |
collection | DOAJ |
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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language | English |
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publishDate | 2015-11-01 |
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series | Toxins |
spelling | doaj.art-48224fcba03b4554a5825704a11df2d32022-12-22T02:20:10ZengMDPI AGToxins2072-66512015-11-017114817483110.3390/toxins7114817toxins7114817Diverse Profiles of Ricin-Cell Interactions in the Lung Following Intranasal Exposure to RicinAnita Sapoznikov0Reut Falach1Ohad Mazor2Ron Alcalay3Yoav Gal4Nehama Seliger5Tamar Sabo6Chanoch Kronman7Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 74100, IsraelDepartment of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 74100, IsraelDepartment of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 74100, IsraelDepartment of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 74100, IsraelDepartment of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 74100, IsraelDepartment of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 74100, IsraelDepartment of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 74100, IsraelDepartment of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 74100, IsraelRicin, 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.http://www.mdpi.com/2072-6651/7/11/4817ricinlungbindingmacrophagesepithelial cellsalveolar type II cells |
spellingShingle | Anita Sapoznikov Reut Falach Ohad Mazor Ron Alcalay Yoav Gal Nehama Seliger Tamar Sabo Chanoch Kronman Diverse Profiles of Ricin-Cell Interactions in the Lung Following Intranasal Exposure to Ricin Toxins ricin lung binding macrophages epithelial cells alveolar type II cells |
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 | ricin lung binding macrophages epithelial cells alveolar type II cells |
url | http://www.mdpi.com/2072-6651/7/11/4817 |
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