Bacillus anthracis lethal toxin induces cell-type-specific cytotoxicity in human lung cell lines.
OBJECTIVE
Inhalational anthrax is caused by the entry of Bacillus anthracis spores into the lung. Inhaled spores are phagocytosed by alveolar macrophages. Bacilli then escape from the macrophage and spread to other cells, initiating a systemic anthrax infection. Based on the pathological studies of primate and human inhalational anthrax cases, it appears that lung tissue injury is a lethal consequence of the disease. Although the cytotoxicity of anthrax lethal toxin to macrophages is well known, it is not clear how anthrax toxin affects the various lung cell types.


RESULTS
Using model cell lines representing different physiological compartments of the lung, we have investigated the cytotoxic effects of anthrax lethal toxin. The cell response was evaluated through MTT metabolism, neutral red uptake, initiation of apoptosis, and expression and binding activity of anthrax toxin receptors. We found that a human small airway epithelial cell line, HSAEC, was susceptible to anthrax lethal toxin. The other cell lines, A549, MRC-5, H358 and SKLU-1, displayed resistance to anthrax lethal toxin-mediated toxicity, although the expression of anthrax toxin receptors was detected in all the cell lines tested.


CONCLUSIONS
Our results indicate that cell-type-specific toxicity may be induced by anthrax lethal toxin in human lung tissues and does not correlate with anthrax toxin receptor expression levels.


CONCLUSIONS
This work suggests that cell-type-specific cytotoxicity of anthrax toxin in lung cells may cause subsequent lung disease progression. It may explain the initial pathogenic step of inhalational anthrax.
Department of Life Science, Sogang University, Shinsu-Dong, Mapo, Seoul, Korea.
N Y
NY
Kim
C I
CI
Kang
G H
GH
Hur
J M
JM
Yang
S
S
Shin
D000818:Animals; D000942:Antigens, Bacterial / Q000633:toxicity*; D017209:Apoptosis; D001427:Bacterial Toxins / Q000633:toxicity*; D002460:Cell Line; D003603:Cytotoxins / Q000633:toxicity; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D003603:Cytotoxins; D018000:Receptors, Peptide; C030325:anthrax toxin; C070309:anthrax toxin receptors
cytotoxicity; inhalational anthrax; lethal toxin; lung cells