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

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 (M?s) 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 M?s 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.

SUBMITTER: Sapoznikov A

PROVIDER: S-EPMC4663535 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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

Sapoznikov Anita A Falach Reut R Mazor Ohad O Alcalay Ron R Gal Yoav Y Seliger Nehama N Sabo Tamar T Kronman Chanoch C

Toxins 20151117 11

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 patter ...[more]

PMID: 26593946

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Project description:Despite the brevity of the procedure, bilateral myringotomy and tympanostomy tube placement (BMT) can result in significant postoperative pain and discomfort. As the procedure is frequently performed without intravenous access, non-parenteral routes of administration are frequently used for analgesia. The current study prospectively compares the efficacy of intranasal (IN) dexmedetomidine with IN fentanyl for children undergoing BMT.This prospective, double-blinded, randomized clinical trial included pediatric patients undergoing BMT. The patients were randomized to receive either IN dexmedetomidine (1 ?g/kg) or fentanyl (2 ?g/kg) after the induction of general anesthesia with sevoflurane. All patients received rectal acetaminophen (40 mg/kg) and the first 50 patients also received premedication with oral midazolam. Postoperative pain and recovery were assessed using pediatric pain and recovery scales, and any adverse effects were monitored for.The study cohort included 100 patients who ranged in age from 1 to 7.7 years and in weight from 8.6 to 37.4 kg. They were divided into 4 groups with 25 patients in each group: (1) midazolam premedication+IN dexmedetomidine; (2) midazolam premedication+IN fentanyl; (3) no premedication+IN dexmedetomidine; and (4) no premedication+IN fentanyl. Pain scores were comparable when comparing groups 2, 3 and 4, but were higher in group 1 (midazolam premedication with IN dexmedetomidine). There was no difference in total time in the post-anesthesia care unit (PACU) or time from arrival in the PACU until hospital discharge between the 4 groups. The heart rate (HR) was significantly lower in group 3 when compared to the other groups at several different times after arrival to the PACU. No clinically significant difference was noted in blood pressure.Following BMT, when no premedication is administered, there was no clinical advantage when comparing IN dexmedetomidine (1 ?g/kg) to IN fentanyl (2 ?g/kg). The addition of oral midazolam as a premedication worsened the outcome measures particularly for children receiving IN dexmedetomidine.

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

Publications

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

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