title: Human serum contains a protease that protects against cytotoxic activity of Bacillus anthracis lethal toxin in vitro.
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.
authors.affiliation: Children's Hospital at Montefiore/Albert Einstein College of Medicine, Division of Pediatric Infectious Diseases, Bronx, NY 10461, USA. dgoldma@aecom.yu.edu
authors.forename: David L
authors.initials: DL
authors.lastname: Goldman
authors.forename: WangYong
authors.initials: W
authors.lastname: Zeng
authors.forename: Johanna
authors.initials: J
authors.lastname: Rivera
authors.forename: Antonio
authors.initials: A
authors.lastname: Nakouzzi
authors.forename: Arturo
authors.initials: A
authors.lastname: Casadevall
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism* / Q000633:toxicity; D001408:Bacillus anthracis; D001427:Bacterial Toxins / Q000378:metabolism* / Q000633:toxicity; D016923:Cell Death; D002460:Cell Line; D006358:Hot Temperature; D006801:Humans; D008264:Macrophages / Q000166:cytology; D051379:Mice; D010447:Peptide Hydrolases / Q000097:blood* / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C030325:anthrax toxin; D010447:Peptide Hydrolases