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Activation of plasminogen by Bacillus anthracis spores and proteases results in down‐regulation of thrombin‐activatable fibrinolysis inhibitor
Author(s) -
Chung MyungChul,
Tonry Jessica H.,
Jorgensen Shelley C.,
Narayanan Aarthi,
Bailey Charles L.,
Popov Serguei G.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.671.1
Subject(s) - plasmin , fibrinolysis , zymogen , proteases , serine protease , microbiology and biotechnology , thrombomodulin , chemistry , thrombin , antifibrinolytic , biology , protease , biochemistry , immunology , enzyme , medicine , platelet , blood loss , surgery , tranexamic acid
Plasminogen is a serine protease zymogen released by the liver and activated by several proteases to regulate mainly fibrinolysis. In this study we examined whether plasminogen activation is involved in Bacillus anthracis pathogenesis. At first, we explored whether secreted anthrax metalloproteases Npr599 and immune inhibitor A (InhA) are involved in pro‐urokinase (pro‐uPA) activation, which leads to plasminogen activation. Exposure of human pro‐uPA to Npr599 and InhA resulted in its proteolytic activation. Western blot analysis performed on liver samples from InhA‐injected mice showed a significant rise in uPA and plasminogen activation when compared to uninfected liver controls. In addition, plasmin(ogen) efficiently bound to spore and cell surfaces in a lysine‐dependent manner. GroEL, enolase, elongation factor Tu and GAPDH were identified as candidate spore surface plasminogen receptors. Spore coated plasmin, as well as Npr599 and InhA degraded thrombin‐activable fibrinolysis inhibitor (TAFI), a plasma zymogen that inhibits fibrinolysis. Moreover, active and inactive TAFI antigen levels were significantly decreased in mouse liver samples without a decrease in gene expression after challenge with the toxigenic Sterne spores and InhA. Taken together, our data suggest that B. anthracis infection down‐regulates TAFI via plasminogen activation and may lead to unregulated fibrinolysis.