Activated protein C ameliorates Bacillus anthracis lethal toxin-induced lethal pathogenesis in rats

Journal of Biomedical Science

Hsin-Hou Chang⁴  Der-Shan Sun⁴  Hung-Chi Lin³  Hsin-Hsien Huang³  Chin-Cheng Lee¹  Te-Sheng Lien⁴  Yung-Luen Shih²  Jyh-Hwa Kau³ 

[1] Department of Pathology and Laboratory Medicine, Shin-Kong Wu-Ho-Su Memorial Hospital, Taipei, Taiwan, ROC;School of Medical Laboratory Science and Biotechnology, Taipei Medical University, Taipei, Taiwan, ROC;Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan, ROC;Department of Molecular Biology and Human Genetics, Tzu-Chi University, Hualien, Taiwan, ROC

关键词: Coagulopathy;    Activated protein C;    Lethal toxin;    Anthrax;   

Others  :  824427
DOI  :  10.1186/1423-0127-19-98

 received in 2012-05-14, accepted in 2012-10-18,  发布年份 2012

【 摘 要 】

Background

Lethal toxin (LT) is a major virulence factor of Bacillus anthracis. Sprague Dawley rats manifest pronounced lung edema and shock after LT treatments, resulting in high mortality. The heart failure that is induced by LT has been suggested to be a principal mechanism of lung edema and mortality in rodents. Since LT-induced death occurs more rapidly in rats than in mice, suggesting that other mechanisms in addition to the heart dysfunction may be contributed to the fast progression of LT-induced pathogenesis in rats. Coagulopathy may contribute to circulatory failure and lung injury. However, the effect of LT on coagulation-induced lung dysfunction is unclear.

Methods

To investigate the involvement of coagulopathy in LT-mediated pathogenesis, the mortality, lung histology and coagulant levels of LT-treated rats were examined. The effects of activated protein C (aPC) on LT-mediated pathogenesis were also evaluated.

Results

Fibrin depositions were detected in the lungs of LT-treated rats, indicating that coagulation was activated. Increased levels of plasma D-dimer and thrombomodulin, and the ameliorative effect of aPC further suggested that the activation of coagulation-fibrinolysis pathways plays a role in LT-mediated pathogenesis in rats. Reduced mortality was associated with decreased plasma levels of D-dimer and thrombomodulin following aPC treatments in rats with LT-mediated pathogenesis.

Conclusions

These findings suggest that the activation of coagulation in lung tissue contributes to mortality in LT-mediated pathogenesis in rats. In addition, anticoagulant aPC may help to develop a feasible therapeutic strategy.

【 授权许可】

   
2012 Kau et al.; licensee BioMed Central Ltd.

【 图 表 】

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