title: 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 (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.
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 74100, Israel. anitas@iibr.gov.il.
authors.forename: Anita
authors.initials: A
authors.lastname: Sapoznikov
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 74100, Israel. reutf@iibr.gov.il.
authors.forename: Reut
authors.initials: R
authors.lastname: Falach
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 74100, Israel. ohadm@iibr.gov.il.
authors.forename: Ohad
authors.initials: O
authors.lastname: Mazor
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 74100, Israel. rona@iibr.gov.il.
authors.forename: Ron
authors.initials: R
authors.lastname: Alcalay
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 74100, Israel. yoavg@iibr.gov.il.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Gal
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 74100, Israel. nehamas@iibr.gov.il.
authors.forename: Nehama
authors.initials: N
authors.lastname: Seliger
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 74100, Israel. tamars@iibr.gov.il.
authors.forename: Tamar
authors.initials: T
authors.lastname: Sabo
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 74100, Israel. chanochk@iibr.gov.il.
authors.forename: Chanoch
authors.initials: C
authors.lastname: Kronman
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D002452:Cell Count; D002619:Chemical Warfare Agents; D003713:Dendritic Cells / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D009504:Neutrophils / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D012276:Ricin / Q000008:administration & dosage* / Q000633:toxicity*
chemical_list: D002619:Chemical Warfare Agents; D011956:Receptors, Cell Surface; D012276:Ricin
keywords: alveolar type II cells; binding; epithelial cells; lung; macrophages; ricin