Total Body Irradiation Mitigates Inflammation and Extends the Therapeutic Time Window for Anti-Ricin Antibody Treatment against Pulmonary Ricinosis in Mice.

Yoav Gal,Moshe Aftalion,Tamar Sabo,Anita Sapoznikov,Chanoch Kronman,Sharon Ehrlich,Reut Falach

doi:10.3390/toxins9090278

Yoav Gal, Moshe Aftalion + Show 5 more

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https://doi.org/10.3390/toxins9090278

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Journal: Toxins	Publication Date: Sep 11, 2017
Citations: 9	License type: CC BY 4.0

Affiliation: Israel Institute for Biological Research

Abstract

Ricin, a highly toxic plant-derived toxin, is considered a potential weapon in biowarfare and bioterrorism due to its pronounced toxicity, high availability, and ease of preparation. Pulmonary exposure to ricin results in the generation of an acute edematous inflammation followed by respiratory insufficiency and death. Massive neutrophil recruitment to the lungs may contribute significantly to ricin-mediated morbidity. In this study, total body irradiation (TBI) served as a non-pharmacological tool to decrease the potential neutrophil-induced lung injury. TBI significantly postponed the time to death of intranasally ricin-intoxicated mice, given that leukopenia remained stable following intoxication. This increase in time to death coincided with a significant reduction in pro-inflammatory marker levels, and led to marked extension of the therapeutic time window for anti-ricin antibody treatment.

Highlights

IntroductionA type II ribosome inactivating protein (RIP), is a toxin derived from the seeds of Ricinus communis (the castor oil plant)
Ricin, a type II ribosome inactivating protein (RIP), is a toxin derived from the seeds of Ricinus communis
Peripheral blood leukopenia (Figure 1A), and neutropenia (Figure 1B), were found to be stable in all mice subjected to total body irradiation (TBI), whether exposed to ricin or not, until day 7 post ricin-exposure in contrast to the prominent leukocytosis and neutrophilia observed in the non-irradiated ricin-intoxicated group

Summary

Introduction

A type II ribosome inactivating protein (RIP), is a toxin derived from the seeds of Ricinus communis (the castor oil plant). The holotoxin consists of two polypeptide chains, ricin toxin. B (RTB) and ricin toxin A (RTA), linked by a single disulfide bond. RTB binds to galactose residues on the surface of cells and mediates the toxin’s cellular internalization, whereas RTA possesses the catalytic activity of ricin [1]. Due to the high availability of the toxin and the relative ease of its production, ricin is considered a biological threat agent [2]. The toxicity of ricin depends on the route of exposure, the inhalational route being considered most fatal [3]. Pulmonary ricinosis comprises two pathological processes, ribosomal depurination and pulmonary inflammation, occurring at the molecular and cellular/tissue levels, respectively

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