1887

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.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.007427-0
2009-06-01
2019-10-23
Loading full text...

Full text loading...

/deliver/fulltext/jmm/58/6/737.html?itemId=/content/journal/jmm/10.1099/jmm.0.007427-0&mimeType=html&fmt=ahah

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]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.007427-0
Loading
/content/journal/jmm/10.1099/jmm.0.007427-0
Loading

Data & Media loading...

Supplements

vol. , part 6, pp. 737-744

Acute-phase protein levels in plasma of spore-challenged mice. Acute-phase protein levels in plasma of InhA-injected mice. Plasma PAI-1 levels in liver harvested from Sterne spore-challenged mice at 72 h and from InhA-injected mice at 6 h post-challenge. Cytokine levels in liver of InhA-injected mice. [PDF](25 KB)



PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error