Characterization of Lung Injury following Abrin Pulmonary Intoxication in Mice: Comparison to Ricin Poisoning

Abrin is a highly toxic protein obtained from the seeds of the rosary pea plant <i>Abrus precatorius</i>, and it is closely related to ricin in terms of its structure and chemical properties. Both toxins inhibit ribosomal function, halt protein synthesis and lead to cellular death. The m...

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Main Authors: Anita Sapoznikov, Yoav Gal, Ron Alcalay, Yentl Evgy, Tamar Sabo, Chanoch Kronman, Reut Falach
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:Toxins
Subjects:
Online Access:https://www.mdpi.com/2072-6651/14/9/614
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author Anita Sapoznikov
Yoav Gal
Ron Alcalay
Yentl Evgy
Tamar Sabo
Chanoch Kronman
Reut Falach
author_facet Anita Sapoznikov
Yoav Gal
Ron Alcalay
Yentl Evgy
Tamar Sabo
Chanoch Kronman
Reut Falach
author_sort Anita Sapoznikov
collection DOAJ
description Abrin is a highly toxic protein obtained from the seeds of the rosary pea plant <i>Abrus precatorius</i>, and it is closely related to ricin in terms of its structure and chemical properties. Both toxins inhibit ribosomal function, halt protein synthesis and lead to cellular death. The major clinical manifestations following pulmonary exposure to these toxins consist of severe lung inflammation and consequent respiratory insufficiency. Despite the high similarity between abrin and ricin in terms of disease progression, the ability to protect mice against these toxins by postexposure antibody-mediated treatment differs significantly, with a markedly higher level of protection achieved against abrin intoxication. In this study, we conducted an in-depth comparison between the kinetics of in vivo abrin and ricin intoxication in a murine model. The data demonstrated differential binding of abrin and ricin to the parenchymal cells of the lungs. Accordingly, toxin-mediated injury to the nonhematopoietic compartment was shown to be markedly lower in the case of abrin intoxication. Thus, profiling of alveolar epithelial cells demonstrated that although toxin-induced damage was restricted to alveolar epithelial type II cells following abrin intoxication, as previously reported for ricin, it was less pronounced. Furthermore, unlike following ricin intoxication, no direct damage was detected in the lung endothelial cell population following abrin exposure. Reduced impairment of intercellular junction molecules following abrin intoxication was detected as well. In contrast, similar damage to the endothelial surface glycocalyx layer was observed for the two toxins. We assume that the reduced damage to the lung stroma, which maintains a higher level of tissue integrity following pulmonary exposure to abrin compared to ricin, contributes to the high efficiency of the anti-abrin antibody treatment at late time points after exposure.
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spelling doaj.art-7a0c3772835641058563a437677889112023-11-23T19:16:46ZengMDPI AGToxins2072-66512022-09-0114961410.3390/toxins14090614Characterization of Lung Injury following Abrin Pulmonary Intoxication in Mice: Comparison to Ricin PoisoningAnita Sapoznikov0Yoav Gal1Ron Alcalay2Yentl Evgy3Tamar Sabo4Chanoch Kronman5Reut Falach6Department 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, IsraelAbrin is a highly toxic protein obtained from the seeds of the rosary pea plant <i>Abrus precatorius</i>, and it is closely related to ricin in terms of its structure and chemical properties. Both toxins inhibit ribosomal function, halt protein synthesis and lead to cellular death. The major clinical manifestations following pulmonary exposure to these toxins consist of severe lung inflammation and consequent respiratory insufficiency. Despite the high similarity between abrin and ricin in terms of disease progression, the ability to protect mice against these toxins by postexposure antibody-mediated treatment differs significantly, with a markedly higher level of protection achieved against abrin intoxication. In this study, we conducted an in-depth comparison between the kinetics of in vivo abrin and ricin intoxication in a murine model. The data demonstrated differential binding of abrin and ricin to the parenchymal cells of the lungs. Accordingly, toxin-mediated injury to the nonhematopoietic compartment was shown to be markedly lower in the case of abrin intoxication. Thus, profiling of alveolar epithelial cells demonstrated that although toxin-induced damage was restricted to alveolar epithelial type II cells following abrin intoxication, as previously reported for ricin, it was less pronounced. Furthermore, unlike following ricin intoxication, no direct damage was detected in the lung endothelial cell population following abrin exposure. Reduced impairment of intercellular junction molecules following abrin intoxication was detected as well. In contrast, similar damage to the endothelial surface glycocalyx layer was observed for the two toxins. We assume that the reduced damage to the lung stroma, which maintains a higher level of tissue integrity following pulmonary exposure to abrin compared to ricin, contributes to the high efficiency of the anti-abrin antibody treatment at late time points after exposure.https://www.mdpi.com/2072-6651/14/9/614abrinricinintranasallungsalveolar epithelial type II cellsneutrophils
spellingShingle Anita Sapoznikov
Yoav Gal
Ron Alcalay
Yentl Evgy
Tamar Sabo
Chanoch Kronman
Reut Falach
Characterization of Lung Injury following Abrin Pulmonary Intoxication in Mice: Comparison to Ricin Poisoning
Toxins
abrin
ricin
intranasal
lungs
alveolar epithelial type II cells
neutrophils
title Characterization of Lung Injury following Abrin Pulmonary Intoxication in Mice: Comparison to Ricin Poisoning
title_full Characterization of Lung Injury following Abrin Pulmonary Intoxication in Mice: Comparison to Ricin Poisoning
title_fullStr Characterization of Lung Injury following Abrin Pulmonary Intoxication in Mice: Comparison to Ricin Poisoning
title_full_unstemmed Characterization of Lung Injury following Abrin Pulmonary Intoxication in Mice: Comparison to Ricin Poisoning
title_short Characterization of Lung Injury following Abrin Pulmonary Intoxication in Mice: Comparison to Ricin Poisoning
title_sort characterization of lung injury following abrin pulmonary intoxication in mice comparison to ricin poisoning
topic abrin
ricin
intranasal
lungs
alveolar epithelial type II cells
neutrophils
url https://www.mdpi.com/2072-6651/14/9/614
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