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Infection and Immunity, June 2006, p. 3455-3462, Vol. 74, No. 6
0019-9567/06/$08.00+0     doi:10.1128/IAI.02088-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Immunoglobulin A Antibodies against Ricin A and B Subunits Protect Epithelial Cells from Ricin Intoxication

Nicholas J. Mantis,1* Carolyn R. McGuinness,1 Oluwakemi Sonuyi,2 Gary Edwards,1 and Stephanie A. Farrant2

Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, New York 12208,1 Gastrointestinal Cell Biology Laboratory, Children's Hospital Boston, Boston, Massachusetts 012252

Received 28 December 2005/ Returned for modification 8 February 2006/ Accepted 28 February 2006

Epithelial cells of the respiratory and gastrointestinal tracts are extremely vulnerable to the cytotoxic effects of ricin, a Shiga-like toxin with ribosome-inactivating properties. While mucosal immunity to ricin correlates with secretory immunoglobulin A (IgA) antibody levels in vivo, the potential of IgA to protect epithelial cells from ricin in vitro has not been examined due to the unavailability of well-defined antitoxin IgA antibodies. Here we report the characterization of four monoclonal IgA antibodies (IgA MAbs) produced from the Peyer's patches and mesenteric lymph nodes of BALB/c mice immunized intragastrically with ricin toxoid. Two IgA MAbs (33G2 and 35H6) were active against ricin's lectin subunit (RTB), and two (23D7 and 25A4) reacted with the toxin's enzymatic subunit (RTA). All four IgA MAbs neutralized ricin in a Vero cell cytotoxicity assay, blocked toxin-induced interleukin-8 release by the human monocyte/macrophage cell line 28SC, and protected polarized epithelial cell monolayers from ricin-mediated protein synthesis inhibition. 33G2 and 35H6 reduced ricin binding to the luminal surfaces of human intestinal epithelial cells to undetectable levels in tissue section overlay assays, whereas 23D7 had no effect on toxin attachment. 23D7 and 25A4 did, however, reduce ricin transcytosis across MDCK II cell monolayers, possibly by interfering with intracellular toxin transport. We conclude that IgA antibodies against RTA and RTB can protect mucosal epithelial cells from ricin intoxication.

* Corresponding author. Mailing address: Division of Infectious Disease, Wadsworth Center, N.Y. State Department of Health, 120 New Scotland Avenue, Albany, NY 12208. Phone: (518) 402-2750. Fax: (518) 402-4773. E-mail: nmantis{at}wadsworth.org.

Editor: A. D. O'Brien

Infection and Immunity, June 2006, p. 3455-3462, Vol. 74, No. 6
0019-9567/06/$08.00+0     doi:10.1128/IAI.02088-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Surendranath, K., Karande, A. A. (2008). A Neutralizing Antibody to the A Chain of Abrin Inhibits Abrin Toxicity both In Vitro and In Vivo. CVI 15: 737-743 [Abstract] [Full Text]  
  • Yoder, J. M., Aslam, R. U., Mantis, N. J. (2007). Evidence for Widespread Epithelial Damage and Coincident Production of Monocyte Chemotactic Protein 1 in a Murine Model of Intestinal Ricin Intoxication. Infect. Immun. 75: 1745-1750 [Abstract] [Full Text]  
  • McGuinness, C. R., Mantis, N. J. (2006). Characterization of a Novel High-Affinity Monoclonal Immunoglobulin G Antibody against the Ricin B Subunit.. Infect. Immun. 74: 3463-3470 [Abstract] [Full Text]  


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