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Diverse profiles of ricin-cell interactions in the lung following intranasal exposure to ricin.

Sapoznikov A, Falach R, Mazor O, Alcalay R, Gal Y, Seliger N, Sabo T, Kronman C - Toxins (Basel) (2015)

Bottom Line: Neutrophils, which were massively recruited to the intoxicated lung, were refractive to toxin binding.The differential binding and cell-elimination patterns observed may stem from dissimilar accessibility of the toxin to different cells in the lung and may also reflect unequal interactions of the toxin with different cell-surface receptors.The multifaceted interactions observed in this study between ricin and the various cells of the target organ should be considered in the future development of efficient post-exposure countermeasures against ricin intoxication.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 74100, Israel. anitas@iibr.gov.il.

ABSTRACT
Ricin, a plant-derived exotoxin, inhibits protein synthesis by ribosomal inactivation. Due to its wide availability and ease of preparation, ricin is considered a biothreat, foremost by respiratory exposure. We examined the in vivo interactions between ricin and cells of the lungs in mice intranasally exposed to the toxin and revealed multi-phasic cell-type-dependent binding profiles. While macrophages (MΦs) and dendritic cells (DCs) displayed biphasic binding to ricin, monophasic binding patterns were observed for other cell types; epithelial cells displayed early binding, while B cells and endothelial cells bound toxin late after intoxication. Neutrophils, which were massively recruited to the intoxicated lung, were refractive to toxin binding. Although epithelial cells bound ricin as early as MΦs and DCs, their rates of elimination differed considerably; a reduction in epithelial cell counts occurred late after intoxication and was restricted to alveolar type II cells only. The differential binding and cell-elimination patterns observed may stem from dissimilar accessibility of the toxin to different cells in the lung and may also reflect unequal interactions of the toxin with different cell-surface receptors. The multifaceted interactions observed in this study between ricin and the various cells of the target organ should be considered in the future development of efficient post-exposure countermeasures against ricin intoxication.

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Measurement of apoptotic changes in the lung after ricin intoxication. Apoptotic staining (TUNEL, green; DAPI, blue) in naive (left) and non-labeled-ricin-intoxicated mice (six mice per group). Scale bars indicate 20 µm.
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toxins-07-04817-f003: Measurement of apoptotic changes in the lung after ricin intoxication. Apoptotic staining (TUNEL, green; DAPI, blue) in naive (left) and non-labeled-ricin-intoxicated mice (six mice per group). Scale bars indicate 20 µm.

Mentions: Our findings show that ricin binds to cells of the lung in a differential manner, perhaps through different receptors. Upon entry to the cytosol, ricin inhibits protein synthesis by the irreversible inactivation of ribosomes, which in turn leads to cell death. Indeed, massive apoptotic changes were readily detected in the lung tissue at late time points after intoxication (24–72 h; Figure 3). In contrast, apoptosis could not be detected at early time points, suggesting that cell elimination early after intoxication, such as that displayed for MΦs and DCs, stems from necrotic death or pyroptosis.


Diverse profiles of ricin-cell interactions in the lung following intranasal exposure to ricin.

Sapoznikov A, Falach R, Mazor O, Alcalay R, Gal Y, Seliger N, Sabo T, Kronman C - Toxins (Basel) (2015)

Measurement of apoptotic changes in the lung after ricin intoxication. Apoptotic staining (TUNEL, green; DAPI, blue) in naive (left) and non-labeled-ricin-intoxicated mice (six mice per group). Scale bars indicate 20 µm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663535&req=5

toxins-07-04817-f003: Measurement of apoptotic changes in the lung after ricin intoxication. Apoptotic staining (TUNEL, green; DAPI, blue) in naive (left) and non-labeled-ricin-intoxicated mice (six mice per group). Scale bars indicate 20 µm.
Mentions: Our findings show that ricin binds to cells of the lung in a differential manner, perhaps through different receptors. Upon entry to the cytosol, ricin inhibits protein synthesis by the irreversible inactivation of ribosomes, which in turn leads to cell death. Indeed, massive apoptotic changes were readily detected in the lung tissue at late time points after intoxication (24–72 h; Figure 3). In contrast, apoptosis could not be detected at early time points, suggesting that cell elimination early after intoxication, such as that displayed for MΦs and DCs, stems from necrotic death or pyroptosis.

Bottom Line: Neutrophils, which were massively recruited to the intoxicated lung, were refractive to toxin binding.The differential binding and cell-elimination patterns observed may stem from dissimilar accessibility of the toxin to different cells in the lung and may also reflect unequal interactions of the toxin with different cell-surface receptors.The multifaceted interactions observed in this study between ricin and the various cells of the target organ should be considered in the future development of efficient post-exposure countermeasures against ricin intoxication.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 74100, Israel. anitas@iibr.gov.il.

ABSTRACT
Ricin, a plant-derived exotoxin, inhibits protein synthesis by ribosomal inactivation. Due to its wide availability and ease of preparation, ricin is considered a biothreat, foremost by respiratory exposure. We examined the in vivo interactions between ricin and cells of the lungs in mice intranasally exposed to the toxin and revealed multi-phasic cell-type-dependent binding profiles. While macrophages (MΦs) and dendritic cells (DCs) displayed biphasic binding to ricin, monophasic binding patterns were observed for other cell types; epithelial cells displayed early binding, while B cells and endothelial cells bound toxin late after intoxication. Neutrophils, which were massively recruited to the intoxicated lung, were refractive to toxin binding. Although epithelial cells bound ricin as early as MΦs and DCs, their rates of elimination differed considerably; a reduction in epithelial cell counts occurred late after intoxication and was restricted to alveolar type II cells only. The differential binding and cell-elimination patterns observed may stem from dissimilar accessibility of the toxin to different cells in the lung and may also reflect unequal interactions of the toxin with different cell-surface receptors. The multifaceted interactions observed in this study between ricin and the various cells of the target organ should be considered in the future development of efficient post-exposure countermeasures against ricin intoxication.

Show MeSH
Related in: MedlinePlus