Activation of plasminogen activator inhibitor implicates protease InhA in the acute-phase response to Bacillus anthracis infection

M.-C. Chung, S. C. Jorgensen, T. G. Popova, J. H. Tonry, C. L. Bailey, S. G. Popov
2009 Journal of Medical Microbiology  
Anthrax is a zoonotic disease caused by Bacillus anthracis. The infection is associated with inflammation and sepsis, but little is known about the acute-phase response during disease and the nature of the bacterial factors causing it. In this study, we examined the levels of the acutephase proteins (APPs) in comparative experiments using mice challenged with spores and a purified B. anthracis protease InhA as a possible factor mediating the response. A strong increase in the plasma levels of
more » ... Ps such as haptoglobin and serum amyloid A was observed during infection. Protein and mRNA levels of plasminogen activator inhibitor (PAI)-1 in the liver were also increased concurrently with bacterial dissemination at 72 h post-infection. Similar effects were observed at 6 h post injection with InhA. Induction of hepatic transforming growth factor-b1, a PAI-1 inducer, was also found in the liver of InhA-injected mice. PAI-1 elevation by InhA resulted in an increased level of urokinase-type plasminogen activator complex with PAI-1 and a decreased level of D-dimers indicating inhibition of blood fibrinolysis. These results reveal an acute liver response to anthrax infection and provide a plausible pathophysiological link between the host inflammatory response and the pro-thrombotic haemostatic imbalance in the course of disease through PAI-1 induction in the liver. Abbreviations: APP, acute-phase protein; CRP, C-reactive protein; HPG, haptoglobin; HPX, haemopexin; InhA, neutral metalloprotease immune inhibitor A; PAI-1, plasminogen activator inhibitor-1; SAA, serum amyloid A; TGF, transforming growth factor; uPA, urokinase-type plasminogen activator.
doi:10.1099/jmm.0.007427-0 pmid:19429749 fatcat:c5jrgof2frfdxdes57uhrud2py