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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MDPI AG
2022-09-01
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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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