Wu F, Fan S, Martiniuk F, Pincus S, Müller S, Kohler H, Tchou-Wong KM. Protective effects of anti-ricin A-chain antibodies delivered intracellularly against ricin-induced cytotoxicity. World J Biol Chem 2010; 1(5): 188-195 [PMID: 21541003 DOI: 10.4331/wjbc.v1.i5.188]
Corresponding Author of This Article
Dr. Kam-Meng Tchou-Wong, Department of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, United States. tchouk02@nyumc.org
Article-Type of This Article
Original Article
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Feng Wu, Shaoan Fan, Kam-Meng Tchou-Wong, Department of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, United States
Frank Martiniuk, Department of Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, United States
Seth Pincus, Department of Research, Children’s Hospital, 200 Henry Clay Avenue, New Orleans, LA 70118, United States
Sybille Müller, Immpheron, Inc., 5235 Athens-Boonesboro Road, Lexington, KY 40509, United States
Heinz Kohler, Markey Cancer Center, University of Kentucky, 800 Rose Street, Lexington, KY 40536-0096, United States
Author contributions: Wu F and Fan S performed the experiments, analyzed the data and wrote the manuscript; Martiniuk F generated cell-permeable antibodies and performed experiments; Pincus S generated Alexa-labeled ricin and RAC18 antibody; Müller S and Kohler H provided consultation on conjugation of MTS peptide to antibodies; Tchou-Wong KM designed and supervised the studies and critically revised and reviewed the manuscript.
Supported by NIEHS Center Grant ES00260 (Tchou-Wong KM) and NIAID R21 Grant AI059476 (Tchou-Wong KM) from the National Institutes of Health
Correspondence to: Dr. Kam-Meng Tchou-Wong, Department of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, United States. tchouk02@nyumc.org
Telephone: +1-845-7313504 Fax: +1-845-3515472
Received: May 10, 2010 Revised: May 15, 2010 Accepted: May 22, 2010 Published online: May 26, 2010
Abstract
AIM: To evaluate the ability of anti-ricin A-chain antibodies, delivered intracellularly, to protect against ricin-induced cytotoxicity in RAW264.7 cells.
METHODS: Anti-deglycosylated ricin A-chain antibody and RAC18 anti-ricin A-chain monoclonal antibody were delivered intracellularly by encapsulating in liposomes or via conjugation with the cell-penetrating MTS-transport peptide. RAW264.7 cells were incubated with these antibodies either before or after ricin exposure. The changes in cytotoxicity were estimated by MTT assay. Co-localization of internalized antibody and ricin was evaluated by fluorescence microscopy.
RESULTS: Internalized antibodies significantly increased cell viability either before or after ricin exposure compared to the unconjugated antibodies. Fluorescence microscopy confirmed the co-localization of internalized antibodies and ricin inside the cells.
CONCLUSION: Intracellular delivery of antibodies to neutralize the ricin toxin after cellular uptake supports the potential use of cell-permeable antibodies for post-exposure treatment of ricin intoxication.
