Antibody treatment against pulmonary exposure to abrin confers significantly higher levels of protection than treatment against ricin intoxication

Sabo, Tamar; Gal, Yoav; Elhanany, Eitan; Sapoznikov, Anita; Falach, Reut; Mazor, Ohad; Kronman, Chanoch

doi:10.1016/j.toxlet.2015.06.003

Cited by 28 publications

(34 citation statements)

References 26 publications

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“…The clinical manifestation following intranasal exposure of mice to the two toxins is also very similar (Gal et al, 2014;Sabo et al, 2015). Despite these similarities, extensive studies carried out in our laboratory demonstrated that the ability to protect mice against the two toxins by post-exposure antibody treatment, differs radically.…”

Section: Quantitative Comparison Of the In-vivo Enzymatic Activities mentioning

confidence: 89%

“…Mice were anesthetized by an intraperitoneal injection of ketamine (1.9 mg/mouse) and xylazine (0.19 mg/ mouse), and were intranasally intoxicated with 2LD 50 of crude ricin or abrin. LD 50 values of ricin and abrin were previously determined to be 3.5 (95% confidence intervals of 2.3-4.4) and 4.0 (95% confidence intervals of 3.43-4.7) mg/kg body weight, respectively (Gal et al, 2014;Sabo et al, 2015).…”

Section: Animal Studiesmentioning

confidence: 99%

“…Toxins were prepared as previously described (Gal et al, 2014;Sapoznikov et al, 2015;Sabo et al, 2015). Briefly, seeds of Ricinus communis or Abrus precatorius were homogenized in a Waring blender in 5% acetic acid/phosphate buffer (Na2 HPO4, pH 7.4) the homogenate was centrifuged and the clarified supernatant containing the toxin was subjected to ammonium sulphate precipitation (60% and 80% saturation, for ricin and abrin, respectively).…”

Section: Ricin and Abrin Preparationmentioning

confidence: 99%

“…Halfmaximal effective concentrations (EC 50 ) of ricin and abrin were determined to be 0.14 AE 0.05 and 0.1 AE 0.03 ng/ml, respectively (Gal et al, 2014;Sabo et al, 2015).…”

Section: Ricin and Abrin Preparationmentioning

confidence: 99%

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Quantitative profiling of the in vivo enzymatic activity of ricin reveals disparate depurination of different pulmonary cell types

et al. 2016

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Section: Quantitative Comparison Of the In-vivo Enzymatic Activities mentioning

confidence: 89%

Section: Animal Studiesmentioning

confidence: 99%

Section: Ricin and Abrin Preparationmentioning

confidence: 99%

“…Halfmaximal effective concentrations (EC 50 ) of ricin and abrin were determined to be 0.14 AE 0.05 and 0.1 AE 0.03 ng/ml, respectively (Gal et al, 2014;Sabo et al, 2015).…”

Section: Ricin and Abrin Preparationmentioning

confidence: 99%

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Quantitative profiling of the in vivo enzymatic activity of ricin reveals disparate depurination of different pulmonary cell types

et al. 2016

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“…These cells infiltrate to the tissue early after exposure, accumulate over time (17,26), and actively secrete damage mediators, such as neutrophil elastase, metalloproteinases, defensins, and reactive oxygen species (ROS), all of which induce and enhance tissue injury (27). Increased IL-10 levels were suggested to reduce lung neutrophil content (23,25).…”

Section: Discussionmentioning

confidence: 99%

Potent Antiedematous and Protective Effects of Ciprofloxacin in Pulmonary Ricinosis

Gal

Sapoznikov

Falach

et al. 2016

Antimicrob Agents Chemother

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The plant toxin ricin is considered a biological threat agent of concern and is most toxic when inhaled. Pulmonary exposure to a lethal dose of ricin can be redressed by treatment with antiricin antibodies; however, late antitoxin intervention is of limited efficacy. This limitation is associated with overt lung damage, clinically manifested as severe pulmonary inflammation, which develops over time. Increased evidence indicates that ciprofloxacin, a broad-spectrum antimicrobial agent, possesses immunomodulatory properties. Here we demonstrate that while antiricin antibody administration at late hours after intranasal exposure to ricin confers limited protection to mice, highly efficient protection can be achieved by adding ciprofloxacin to the antibody treatment. We further demonstrate that parameters associated with lung injury, in particular, pulmonary proinflammatory cytokine production, neutrophil migration, and edema, are sharply reduced in ricin-intoxicated mice that were treated with ciprofloxacin. The presented data highlight the potential clinical application of ciprofloxacin as a beneficial immunomodulatory agent in the course of ricin intoxication. Ricin, a type II ribosome-inactivating protein, is a plant toxin derived from the seeds of Ricinus communis (castor beans). The holotoxin consists of two polypeptide chains (A and B) linked by a disulfide bond. The B chain is a lectin, which binds to galactose residues on the cell surface. The A chain possesses RNA Nglycosidase activity that irreversibly inactivates the 28S rRNA of the mammalian 60S ribosome subunit, subsequently arresting cell protein synthesis (1). Due to its high availability and relative ease of production, ricin is considered a biological threat agent (2). The toxicity of ricin depends on the route of exposure, inhalatory exposure being considered the most severe (3). Pathological studies of pulmonary ricin intoxication have demonstrated that injury is confined mostly to the lungs (4) and characterized by a local cytokine storm, massive neutrophil recruitment, increased prooxidant enzyme activity, and development of proteinaceous pulmonary edema, subsequently resulting in respiratory failure and death (4, 5).Prophylactic antiricin vaccines are being developed (6), yet postexposure medical countermeasures are needed for treatment of unvaccinated victims after pulmonary exposure to lethal doses of the toxin. Previous studies have examined the possibility of protecting animals against pulmonary ricinosis by passive immunization with polyclonal antiricin antibodies; nevertheless, under this mode of protection, survival rates declined sharply in correlation with antitoxin administration timing following intoxication, so that antiricin antibodies administered 24 h after exposure gave rise to limited rates of survival (5, 7). At this late time point, the pathophysiological condition of some of the intoxicated mice may have deteriorated so that the loss of function of the lungs is irreversible. Conversely, we previously showed that higher sur...

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Ribosome-Inactivating Proteins: An Overview

Stirpe¹,

Gilabert-Oriol²

2017

Toxinology

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Antibody treatment against pulmonary exposure to abrin confers significantly higher levels of protection than treatment against ricin intoxication

Cited by 28 publications

References 26 publications

Quantitative profiling of the in vivo enzymatic activity of ricin reveals disparate depurination of different pulmonary cell types

Quantitative profiling of the in vivo enzymatic activity of ricin reveals disparate depurination of different pulmonary cell types

Potent Antiedematous and Protective Effects of Ciprofloxacin in Pulmonary Ricinosis

Ribosome-Inactivating Proteins: An Overview

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