Human serum contains a protease that protects against cytotoxic activity of Bacillus anthracis lethal toxin in vitro

David L. Goldman, Wang Yong Zeng, Johanna Rivera, Antonio Nakouzzi, Arturo Casadevall

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)970-973
Number of pages4
JournalClinical and Vaccine Immunology
Volume15
Issue number6
DOIs
Publication statusPublished - Jun 1 2008

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Clinical Biochemistry
  • Microbiology (medical)

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