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Clinical and Vaccine Immunology, June 2008, p. 970-973, Vol. 15, No. 6
1071-412X/08/$08.00+0     doi:10.1128/CVI.00064-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Human Serum Contains a Protease That Protects against Cytotoxic Activity of Bacillus anthracis Lethal Toxin In Vitro{triangledown}

David L. Goldman,1* WangYong Zeng,1 Johanna Rivera,2 Antonio Nakouzzi,2 and Arturo Casadevall2

Children's Hospital at Montefiore/Albert Einstein College of Medicine, Division of Pediatric Infectious Diseases,1 Albert Einstein College of Medicine, Division of Microbiology and Immunology, Bronx, New York2

Received 15 February 2008/ Returned for modification 4 March 2008/ Accepted 18 April 2008

The role of innate immunity in the host response to Bacillus anthracis is poorly understood. We found that normal human serum contains an antitoxin mechanism that is capable of protecting macrophages in vitro from B. anthracis lethal toxin-mediated killing. This protective activity was limited to defined amounts of toxin and was lost by heat treatment or serum dilution. Some person-to-person variation in the protective activity of serum was noted, especially with higher concentrations of lethal toxin. A similar protective activity was found in murine serum, though human serum consistently neutralized more toxin than did murine serum. The protective activities of both murine and human sera correlated with cleavage of the protective antigen into two fragments with approximate molecular sizes of 20 and 50 kDa that were recognized by the monoclonal antibodies 7.5G and 10F4, respectively. This pattern of fragmentation is consistent with cleavage at multiple sites, including the furin-susceptible site. Cleavage was abolished by heat treatment and calcium chelation. These findings highlight a potential role for serum proteases in protection against the lethal toxin of B. anthracis.

* Corresponding author. Mailing address: Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461. Phone: (718) 430-2399. Fax: (718) 430-8701. E-mail: dgoldma{at}aecom.yu.edu

{triangledown} Published ahead of print on 30 April 2008.

Clinical and Vaccine Immunology, June 2008, p. 970-973, Vol. 15, No. 6
1071-412X/08/$08.00+0     doi:10.1128/CVI.00064-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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