Lethal toxin of Bacillus anthracis causes apoptosis of macrophages

Lethal toxin is a major anthrax virulence factor, causing the rapid death of experimental animals. Lethal toxin can enter most cell types, but only certain macrophages and cell lines are susceptible to toxin-mediated cytolysis. We have shown that in murine RAW 264.7 cells, sublytic amounts of lethal...

Full description

Saved in:
Bibliographic Details
Published in:Biochemical and biophysical research communications 2002-04, Vol.293 (1), p.349-355
Main Authors: Popov, Serguei G, Villasmil, Rafael, Bernardi, Jessica, Grene, Edith, Cardwell, Jennifer, Wu, Aiguo, Alibek, Darya, Bailey, Charles, Alibek, Ken
Format: Article
Language:English
Subjects:
Animals
Anthrax
Antigens, Bacterial
Apoptosis
Apoptosis - drug effects
Bacillus anthracis
Bacterial Toxins
Bactericidal activity
Carrier Proteins - antagonists & inhibitors
Carrier Proteins - toxicity
Caspase 3
Caspase 8
Caspase 9
Caspase Inhibitors
Cell Line
Cysteine Proteinase Inhibitors - pharmacology
Lethal toxin
Macrophages
Macrophages - cytology
Macrophages - drug effects
Macrophages - physiology
Mice
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Lethal toxin is a major anthrax virulence factor, causing the rapid death of experimental animals. Lethal toxin can enter most cell types, but only certain macrophages and cell lines are susceptible to toxin-mediated cytolysis. We have shown that in murine RAW 264.7 cells, sublytic amounts of lethal toxin trigger intracellular signaling events typical for apoptosis, including changes in membrane permeability, loss of mitochondrial membrane potential, and DNA fragmentation. The cells were protected from the toxin by specific inhibitors of caspase-1, -2, -3, -4, -6, and -8. Phagocytic activity of macrophages was inhibited by sublytic concentrations of lethal toxin. Infection of cells with anthrax (Sterne) spores impaired their bactericidal capacity, which could be reversed by a lethal toxin inhibitor, bestatin. We suggest that apoptosis rather than direct lysis is biologically relevant to lethal toxin intracellular activity.
ISSN:0006-291X
1090-2104
DOI:10.1016/S0006-291X(02)00227-9