Activation of plasminogen activator inhibitor implicates protease InhA in the acute-phase response to Bacillus anthracis infection.
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 acute-phase 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 APPs 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-beta1, 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.
National Center for Biodefense and Infectious Diseases, George Mason University, 10900 University Blvd, Manassas, VA 20110, USA.
Myung-Chul
MC
Chung
National Center for Biodefense and Infectious Diseases, George Mason University, 10900 University Blvd, Manassas, VA 20110, USA.
Shelley C
SC
Jorgensen
National Center for Biodefense and Infectious Diseases, George Mason University, 10900 University Blvd, Manassas, VA 20110, USA.
Taissia G
TG
Popova
National Center for Biodefense and Infectious Diseases, George Mason University, 10900 University Blvd, Manassas, VA 20110, USA.
Jessica H
JH
Tonry
National Center for Biodefense and Infectious Diseases, George Mason University, 10900 University Blvd, Manassas, VA 20110, USA.
Charles L
CL
Bailey
National Center for Biodefense and Infectious Diseases, George Mason University, 10900 University Blvd, Manassas, VA 20110, USA.
Serguei G
SG
Popov
D000209:Acute-Phase Proteins / Q000378:metabolism*; D000818:Animals; D000881:Anthrax / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D001408:Bacillus anthracis / Q000201:enzymology* / Q000472:pathogenicity* / Q000502:physiology; D001426:Bacterial Proteins / Q000378:metabolism; D005260:Female; D006242:Haptoglobins / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000382:microbiology; D008099:Liver / Q000378:metabolism; D045726:Metalloproteases / Q000378:metabolism*; D051379:Mice; D008811:Mice, Inbred DBA; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D013171:Spores, Bacterial / Q000472:pathogenicity; D013927:Thrombosis / Q000276:immunology / Q000382:microbiology; D015854:Up-Regulation
D000209:Acute-Phase Proteins; D001426:Bacterial Proteins; D006242:Haptoglobins; D017395:Plasminogen Activator Inhibitor 1; D045726:Metalloproteases