The Histological Changes Produced by Ricin and Abrin Intoxications

Flexner, Simon

doi:10.1084/jem.2.2.197

Cited by 50 publications

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“…However, many reports demonstrate that ricin toxicity results not only from inhibition of protein synthesis but also from cell apoptosis, and release of cytokine inflammatory mediators [123][124][125][126][127]. One of the earliest reports that ricin is capable of inducing cell death by apoptosis came from studies carried by Griffiths et al in 1987 [124].…”

Section: Action Of Ricin and Corresponding Immunotoxins On Ribosomes mentioning

confidence: 99%

Ricin and Ricin-Containing Immunotoxins: Insights into Intracellular Transport and Mechanism of action in Vitro

Słomińska-Wojewódzka

Sandvig

2013

Antibodies

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Ricin is a type II ribosome inactivating protein (RIP) isolated from castor beans. Its high toxicity classifies it as a possible biological weapon. On the other hand, ricin linked to specific monoclonal antibodies or used in other conjugates has powerful medical applications. Ricin consists of an A-chain (RTA) that damages ribosomes and inhibits protein synthesis, and a B-chain that plays a role in binding and cellular uptake. A number of recent studies have demonstrated that ricin-induced inhibition of protein synthesis is not the only mechanism responsible for cell death. It turns out that ricin is able to induce apoptosis in different cell lines and multiple organs in animals. However, the molecular link between protein synthesis inhibition and ricin-dependent triggering of apoptotic cell death is unclear. This review describes the intracellular transport of ricin and ricin-based immunotoxins and their mechanism of action in different non-malignant and cancer cell lines. Moreover, various ricin-containing immunotoxins, their composition, medical applications and side-effects will be described and discussed. Understanding the mechanism of action of ricin-based immunotoxins will facilitate construction of effectively acting immunotoxins that can be used in the clinic for cancer treatment

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Section: Action Of Ricin and Corresponding Immunotoxins On Ribosomes mentioning

confidence: 99%

Ricin and Ricin-Containing Immunotoxins: Insights into Intracellular Transport and Mechanism of action in Vitro

Słomińska-Wojewódzka

Sandvig

2013

Antibodies

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“…In 1897, for example, Simon Flexner, describing the histological changes in rabbits and guinea pigs associated with parenteral ricin exposure, noted that “Of all the constituents of the intestinal mucosa, the one that feels the most severe effects of the poison is the epithelium” (Flexner 1897). Epithelial damage is also observed when the toxin is administered perorally or by gavage, although relatively high doses (1–10 mg/kg) of ricin are required to provoke a reproducible response (Leek et al 1989; Mantis et al 2011; Neal et al 2011; Sekine et al 1986; Smallshaw et al 2007; Yoder et al 2007).…”

Section: Mucosal Immunity To Ricinmentioning

confidence: 99%

Immunity to Ricin: Fundamental Insights into Toxin–Antibody Interactions

O’Hara

Yermakova

Mantis

2011

Current Topics in Microbiology and Immunology

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Ricin toxin is an extraordinarily potent inducer of cell death and inflammation. Ricin is also a potent provocateur of the humoral immune system, eliciting a mixture of neutralizing, non-neutralizing and even toxin-enhancing antibodies. The characterization of dozens of monoclonal antibodies (mAbs) against the toxin's enzymatic (RTA) and binding (RTB) subunits has begun to reveal fundamental insights into the underlying mechanisms by which antibodies neutralize (or fail to neutralize) ricin in systemic and mucosal compartments. This information has had immediate applications in the design, development and evaluation of ricin subunit vaccines and immunotherapeutics.

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“…The sensitivity of the intestinal epithelium to ricin, and related RNA N-glycosidases, has been recognized for more than 100 years [9]. Rats challenged with ricin by gavage, for example, develop dose-dependent lesions in the proximal small intestine, including widespread villus atrophy, crypt elongation, sloughing of the epithelium, and occasional infiltration of inflammatory cells, including eosinophils and neutrophils [10–13].…”

Section: Introductionmentioning

confidence: 99%

Vaccine-induced intestinal immunity to ricin toxin in the absence of secretory IgA

Neal¹,

McCarthy²,

Morris³

et al. 2011

Vaccine

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The RNA N-glycosidase ribosome inactivating proteins (RIPs) constitute a ubiquitous family of plant-and bacterium-derived toxins that includes the category B select agents ricin, abrin and shiga toxin. While these toxins are potent inducers of intestinal epithelial cell death and inflammation, very little is known about the mechanisms underlying mucosal immunity to these toxins. In the present study, we report that secretory IgA (SIgA) antibodies are not required for intestinal immunity to ricin, as evidenced by the fact that mice devoid of SIgA, due to a mutation in the polymeric immunoglobulin receptor, were impervious to the effects of intragastric toxin challenge following ricin toxoid immunization. Furthermore, parenteral administration of ricinspecific monoclonal IgGs, directed against either ricin's enzymatic subunit (RTA) or binding subunit (RTB), to wild type mice were as effective as monoclonal IgAs with comparable specificities in imparting intestinal immunity to ricin. These data are consistent with reports from others demonstrating that immunization of mice by routes known not to induce mucosal antibody responses (e.g., intramuscular and intradermal) are sufficient to elicit protection against both systemic and mucosal ricin challenge.

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The Histological Changes Produced by Ricin and Abrin Intoxications

Cited by 50 publications

References 0 publications

Ricin and Ricin-Containing Immunotoxins: Insights into Intracellular Transport and Mechanism of action in Vitro

Ricin and Ricin-Containing Immunotoxins: Insights into Intracellular Transport and Mechanism of action in Vitro

Immunity to Ricin: Fundamental Insights into Toxin–Antibody Interactions

Vaccine-induced intestinal immunity to ricin toxin in the absence of secretory IgA

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