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

Area of Science:

• Pathology
• Toxicology
• Hematology

Background:

• Lethal toxin (LT) from Bacillus anthracis causes severe lung edema and shock in rats.
• While heart failure is a known mechanism, rapid LT-induced mortality in rats suggests additional contributing factors.
• The role of coagulopathy in LT-mediated lung dysfunction and mortality remains unclear.

Purpose of the Study:

• To investigate the involvement of coagulopathy in LT-mediated pathogenesis in rats.
• To assess the impact of LT on coagulation and fibrinolysis pathways.
• To evaluate the therapeutic potential of activated protein C (aPC) in LT-induced pathogenesis.

Main Methods:

• Examined mortality rates, lung histology, and plasma coagulant levels in LT-treated rats.
• Investigated the effects of activated protein C (aPC) on LT-mediated pathogenesis.
• Analyzed fibrin deposition, D-dimer, and thrombomodulin levels.

Main Results:

• Fibrin depositions were observed in the lungs of LT-treated rats, indicating activated coagulation.
• Elevated plasma D-dimer and thrombomodulin levels were detected in LT-treated rats.
• Treatment with aPC ameliorated LT-induced pathogenesis, reducing mortality and decreasing D-dimer and thrombomodulin levels.

Conclusions:

• Activation of coagulation in lung tissue contributes significantly to mortality in LT-mediated pathogenesis in rats.
• Anticoagulant therapy with aPC shows promise as a therapeutic strategy for anthrax toxin-induced lung injury.
• These findings highlight the critical role of the coagulation-fibrinolysis system in anthrax pathogenesis.