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

Abstract

Anthrax is a zoonotic disease caused by . 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 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-1, 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.

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2009-06-01
2024-03-29
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References

  1. Ascenzi P., Fasano M. 2007; Heme-hemopexin: a ‘chronosteric' heme-protein. IUBMB Life 59:700–708 [CrossRef]
    [Google Scholar]
  2. Baumann H., Gauldie J. 1994; The acute phase response. Immunol Today 15:74–80 [CrossRef]
    [Google Scholar]
  3. Beaufort N., Wojciechowski P., Sommerhoff C. P., Szmyd G., Dubin G., Eick S., Kellermann J., Schmitt M., Potempa J., Magdolen V. 2008; The human fibrinolytic system is a target for the staphylococcal metalloprotease aureolysin. Biochem J 410:157–165 [CrossRef]
    [Google Scholar]
  4. Biemond B. J., Levi M., Ten Cate H., van der Poll T., Büller H. R., Hack C. E., Ten Cate J. W. 1995; Plasminogen activator and plasminogen activator inhibitor I release during experimental endotoxaemia in chimpanzees: effect of interventions in the cytokine and coagulation cascades. Clin Sci (Lond 88:587–594
    [Google Scholar]
  5. Birgel M., Gottschling-Zeller H., Röhrig K., Hauner H. 2000; Role of cytokines in the regulation of plasminogen activator inhibitor-1 expression and secretion in newly differentiated subcutaneous human adipocytes. Arterioscler Thromb Vasc Biol 20:1682–1687 [CrossRef]
    [Google Scholar]
  6. Chitlaru T., Gat O., Grosfeld H., Inbar I., Gozlan Y., Shafferman A. 2007; Identification of in vivo -expressed immunogenic proteins by serological proteome analysis of the Bacillus anthracis secretome. Infect Immun 75:2841–2852 [CrossRef]
    [Google Scholar]
  7. Chung M. C., Popova T. G., Millis B. A., Mukherjee D. V., Zhou W., Liotta L. A., Petricoin E. F., Chandhoke V., Bailey C., Popov S. G. 2006; Secreted neutral metalloproteases of Bacillus anthracis as candidate pathogenic factors. J Biol Chem 281:31408–31418 [CrossRef]
    [Google Scholar]
  8. Chung M. C., Jorgensen S. C., Popova T. G., Bailey C. L., Popov S. G. 2008a; Neutrophil elastase and syndecan shedding contribute to antithrombin depletion in murine anthrax. FEMS Immunol Med Microbiol 54:309–318 [CrossRef]
    [Google Scholar]
  9. Chung M. C., Popova T. G., Jorgensen S. C., Dong L., Chandhoke V., Bailey C. L., Popov S. G. 2008b; Degradation of circulating von Willebrand factor and its regulator ADAMTS13 implicates secreted Bacillus anthracis metalloproteases in anthrax consumptive coagulopathy. J Biol Chem 283:9531–9542 [CrossRef]
    [Google Scholar]
  10. Dong J., Fujii S., Goto D., Furumoto T., Kaneko T., Zaman T. A., Nakai Y., Mishima T., Imagawa S., Kitabatake A. 2003; Increased expression of plasminogen activator inhibitor-1 by mediators of the acute phase response: a potential progenitor of vasculopathy in hypertensives. Hypertens Res 26:723–729 [CrossRef]
    [Google Scholar]
  11. Duan X. 2005; Immunodepletion of albumin for two-dimensional gel detection of new mouse acute-phase protein and other plasma proteins. Proteomics 5:3991–4000 [CrossRef]
    [Google Scholar]
  12. Gruys E., Van Ederen A. M., Alsemgeest S. P. M., Kalsbeek H. C., Wensing T. 1993; Acute-phase protein values in blood of cattle as indicator of animals with pathological processes. Arch Lebensmittelhyg 44:107–111
    [Google Scholar]
  13. Gruys E., Obwolo M. J., Toussaint M. J. M. 1994; Diagnostic significance of the major acute phase proteins in veterinary clinical chemistry: a review. Vet Bull 64:1009–1018
    [Google Scholar]
  14. Gutierrez F. R., Lalu M. M., Mariano F. S., Milanezi C. M., Cena J., Gerlach R. F., Santos J. E., Torres-Dueñas D., Cunha F. Q. other authors 2008; Increased activities of cardiac matrix metalloproteinases matrix metalloproteinase (MMP)-2 and MMP-9 are associated with mortality during the acute phase of experimental Trypanosoma cruzi infection. J Infect Dis 197:1468–1476 [CrossRef]
    [Google Scholar]
  15. Heffernan B. J., Thomason B., Herring-Palmer A., Hanna P. 2007; Bacillus anthracis anthrolysin O and three phospholipases C are functionally redundant in a murine model of inhalation anthrax. FEMS Microbiol Lett 271:98–105 [CrossRef]
    [Google Scholar]
  16. Hoffman J. S., Benditt E. P. 1982; Changes in high density lipoprotein content following endotoxin administration in the mouse: formation of serum amyloid protein-rich subfractions. J Biol Chem 257:10510–10517
    [Google Scholar]
  17. Kastrup C. J., Boedicker J. Q., Pomerantsev A. P., Moayeri M., Bian Y., Pompano R. R., Kline T. R., Sylvestre P., Shen F. other authors 2008; Spatial localization of bacteria controls coagulation of human blood by ‘quorum acting'. Nat Chem Biol 4:742–750 [CrossRef]
    [Google Scholar]
  18. Komori Y., Nonogaki T., Nikai T. 2001; Hemorrhagic activity and muscle damaging effect of Pseudomonas aeruginosa metalloproteinase (elastase). Toxicon 39:1327–1332 [CrossRef]
    [Google Scholar]
  19. Kruithof E. K. 1988; Plasminogen activator inhibitors: a review. Enzyme 40:113–121
    [Google Scholar]
  20. Kruithof E. K., Gudinchet A., Bachmann F. 1988; Plasminogen activator inhibitor 1 and plasminogen activator inhibitor 2 in various disease states. Thromb Haemost 59:7–12
    [Google Scholar]
  21. Kushner I., Mackiewicz A. 1987; Acute phase proteins as disease markers. Dis Markers 5:1–11
    [Google Scholar]
  22. Lee C.-C., Huang T.-S. 2005; Plasminogen activator inhibitor-1: the expression, biological functions, and effects on tumorigenesis and tumor cell adhesion and migration. J Cancer Mol 1:25–36
    [Google Scholar]
  23. Lin W.-W., Karin M. 2007; A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest 117:1175–1183 [CrossRef]
    [Google Scholar]
  24. Liu R. M. 2008; Oxidative stress, plasminogen activator inhibitor 1, and lung fibrosis. Antioxid Redox Signal 10:303–319 [CrossRef]
    [Google Scholar]
  25. Moayeri M., Haines D., Young H. A., Leppla S. H. 2003; Bacillus anthracis lethal toxin induces TNF-alpha-independent hypoxia-mediated toxicity in mice. J Clin Invest 112:670–682 [CrossRef]
    [Google Scholar]
  26. Narasaki R., Kuribayashi H., Shimizu K., Imamura D., Sato T., Hasumi K. 2005; Bacillolysin MA, a novel bacterial metalloproteinase that produces angiostatin-like fragments from plasminogen and activates protease zymogens in the coagulation and fibrinolysis systems. J Biol Chem 280:14278–14287 [CrossRef]
    [Google Scholar]
  27. Park J. M., Ng V. H., Maeda S., Rest R. F., Karin M. 2004; Anthrolysin O and other gram-positive cytolysins are toll-like receptor 4 agonists. J Exp Med 200:1647–1655 [CrossRef]
    [Google Scholar]
  28. Popov S. G., Popova T. G., Grene E., Klotz F., Cardwell J., Bradburne C., Jama Y., Maland M., Wells J. other authors 2004; Systemic cytokine response in murine anthrax. Cell Microbiol 6:225–233 [CrossRef]
    [Google Scholar]
  29. Rocha E., Páramo J. A., Montes R., Panizo C. 1998; Acute generalized, widespread bleeding. Diagnosis and management. Haematologica 83:1024–1037
    [Google Scholar]
  30. Sherer K., Li Y., Cui X., Eichacker P. Q. 2007; Lethal and edema toxins in the pathogenesis of Bacillus anthracis septic shock: implications for therapy. Am J Respir Crit Care Med 175:211–221 [CrossRef]
    [Google Scholar]
  31. Stearns-Kurosawa D. J., Lupu F., Taylor F. B., Kinasewitz G., Kurosawa S. 2006; Sepsis and pathophysiology of anthrax in a nonhuman primate model. Am J Pathol 169:433–444 [CrossRef]
    [Google Scholar]
  32. Steel D. M., Whitehead A. S. 1994; The major acute phase reactants: C-reactive protein, serum amyloid P component and serum amyloid A protein. Immunol Today 15:81–88 [CrossRef]
    [Google Scholar]
  33. Sutterwala F. S., Ogura Y., Flavell R. A. 2007; The inflammasome in pathogen recognition and inflammation. J Leukoc Biol 82:259–264 [CrossRef]
    [Google Scholar]
  34. Theilgaard-Mönch K., Jacobsen L. C., Nielsen M. J., Rasmussen T., Udby L., Gharib M., Arkwright P. D., Gombart A. F., Calafat J. other authors 2006; Haptoglobin is synthesized during granulocyte differentiation, stored in specific granules, and released by neutrophils in response to activation. Blood 108:353–361 [CrossRef]
    [Google Scholar]
  35. Thompson D., Milford-Ward A., Whicher J. T. 1992; The value of acute phase protein measurements in clinical practice. Ann Clin Biochem 29:123–131 [CrossRef]
    [Google Scholar]
  36. Tilg H., Dinarello C. A., Mier J. 1997; IL-6 and APP: anti-inflammatory and immunosuppressive mediators. Immunol Today 18:428–432 [CrossRef]
    [Google Scholar]
  37. Tolosano E., Fagoonee S., Hirsch E., Berger F. G., Baumann H., Silengo L., Altruda F. 2002; Enhanced splenomegaly and severe liver inflammation in haptoglobin/hemopexin double-null mice after acute hemolysis. Blood 100:4201–4208 [CrossRef]
    [Google Scholar]
  38. Vassalli J. D., Sappino A. P., Belin D. 1991; The plasminogen activator/plasmin system. J Clin Invest 88:1067–1072 [CrossRef]
    [Google Scholar]
  39. Wait R. 2005; Reference maps of mouse serum acute-phase proteins: changes with LPS-induced inflammation and apolipoprotein A-I and A-II transgenes. Proteomics 5:4245–4253 [CrossRef]
    [Google Scholar]
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