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

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

Research output: Contribution to journalArticle

8 Citations (Scopus)

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
StatePublished - Jun 2008

Fingerprint

Peptide Hydrolases
Heat treatment
Furin
Antitoxins
Macrophages
Bacilli
Chelation
Serum
Dilution
Monoclonal Antibodies
Calcium
Antigens
Hot Temperature
Bacillus anthracis
anthrax toxin
In Vitro Techniques
Innate Immunity

ASJC Scopus subject areas

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

Cite this

Human serum contains a protease that protects against cytotoxic activity of Bacillus anthracis lethal toxin in vitro. / Goldman, David L.; Zeng, WangYong; Rivera, Johanna; Nakouzzi, Antonio; Casadevall, Arturo.

In: Clinical and Vaccine Immunology, Vol. 15, No. 6, 06.2008, p. 970-973.

Research output: Contribution to journalArticle

@article{b78eceb8b0224529be7426290892dd19,
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.",
author = "Goldman, {David L.} and WangYong Zeng and Johanna Rivera and Antonio Nakouzzi and Arturo Casadevall",
year = "2008",
month = "6",
doi = "10.1128/CVI.00064-08",
language = "English (US)",
volume = "15",
pages = "970--973",
journal = "Clinical and Vaccine Immunology",
issn = "1556-6811",
publisher = "American Society for Microbiology",
number = "6",

}

TY - JOUR

T1 - Human serum contains a protease that protects against cytotoxic activity of Bacillus anthracis lethal toxin in vitro

AU - Goldman, David L.

AU - Zeng, WangYong

AU - Rivera, Johanna

AU - Nakouzzi, Antonio

AU - Casadevall, Arturo

PY - 2008/6

Y1 - 2008/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=47049121264&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=47049121264&partnerID=8YFLogxK

U2 - 10.1128/CVI.00064-08

DO - 10.1128/CVI.00064-08

M3 - Article

C2 - 18448623

AN - SCOPUS:47049121264

VL - 15

SP - 970

EP - 973

JO - Clinical and Vaccine Immunology

JF - Clinical and Vaccine Immunology

SN - 1556-6811

IS - 6

ER -