title: Neutralizing Monoclonal Antibodies against Disparate Epitopes on Ricin Toxin's Enzymatic Subunit Interfere with Intracellular Toxin Transport.
abstract: Ricin is a member of the A-B family of bacterial and plant toxins that exploit retrograde trafficking to the Golgi apparatus and endoplasmic reticulum (ER) as a means to deliver their cytotoxic enzymatic subunits into the cytoplasm of mammalian cells. In this study we demonstrate that R70 and SyH7, two well-characterized monoclonal antibodies (mAbs) directed against distinct epitopes on the surface of ricin's enzymatic subunit (RTA), interfere with toxin transport from the plasma membrane to the trans Golgi network. Toxin-mAb complexes formed on the cell surface delayed ricin's egress from EEA-1(+) and Rab7(+) vesicles and enhanced toxin accumulation in LAMP-1(+) vesicles, suggesting the complexes were destined for degradation in lysosomes. Three other RTA-specific neutralizing mAbs against different epitopes were similar to R70 and SyH7 in terms of their effects on ricin retrograde transport. We conclude that interference with toxin retrograde transport may be a hallmark of toxin-neutralizing antibodies directed against disparate epitopes on RTA.
authors.affiliation: Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, NY 12208.|Department of Biomedical Sciences, School of Public Health, University at Albany, Albany, NY 12201.
authors.forename: Anastasiya
authors.initials: A
authors.lastname: Yermakova
authors.affiliation: Department of Molecular Cell Biology, Centre for Cancer Biomedicine, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, Oslo, Norway.
authors.forename: Tove Irene
authors.initials: TI
authors.lastname: Klokk
authors.affiliation: Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, NY 12208.|Department of Biomedical Sciences, School of Public Health, University at Albany, Albany, NY 12201.
authors.forename: Joanne M
authors.initials: JM
authors.lastname: O'Hara
authors.affiliation: Department of Biomedical Sciences, School of Public Health, University at Albany, Albany, NY 12201.|Division of Translational Medicine, Wadsworth Center, New York State Department of Health, Albany, NY 12201.
authors.forename: Richard
authors.initials: R
authors.lastname: Cole
authors.affiliation: Department of Molecular Cell Biology, Centre for Cancer Biomedicine, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, Oslo, Norway.|Department of Biosciences, University of Oslo, Oslo, Norway.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Sandvig
authors.affiliation: Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, NY 12208.|Department of Biomedical Sciences, School of Public Health, University at Albany, Albany, NY 12201.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Mantis
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism*; D000992:Antitoxins / Q000276:immunology / Q000378:metabolism*; D002619:Chemical Warfare Agents / Q000378:metabolism*; D002522:Chlorocebus aethiops; D000939:Epitopes / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D012276:Ricin / Q000276:immunology / Q000378:metabolism*; D014709:Vero Cells
chemical_list: D000911:Antibodies, Monoclonal; D000992:Antitoxins; D002619:Chemical Warfare Agents; D000939:Epitopes; D007155:Immunologic Factors; D012276:Ricin