Anthrax toxin-induced shock in rats is associated with pulmonary edema and hemorrhage

Shu Ru Kuo, Mark C. Willingham, Sarah H. Bour, Elissa A. Andreas, Seong Kyu Park, Carney Jackson, Nicholas S. Duesbery, Stephen H. Leppla, Wei Jen Tang, Arthur E. Frankel

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Bacillus anthracis infections are frequently associated with severe and often irreversible hypotensive shock despite appropriate antibiotics and aggressive hemodynamic and pulmonary support. Based on the observations that the anthrax secreted proteins-protective antigen (PA), lethal factor (LF), and edema factor (EF) also produce shock and mortality in animal models, we chose to characterize further the clinical chemistries and microscopic pathology of toxin treated rats. Groups of three male Sprague Dawley rats received bolus intravenous infusions of PA/LF, PA/EF, LF, or EF alone and blood samples and tissues were collected and assayed for chemistries and tissue pathology. In PA/LF and PA/EF treated animals but not other groups, chemistries showed transaminasemia and elevated lactate dehydrogenase. PA/LF treated animals alone showed elevated hemoglobin and hematocrits; PA/EF treated animals alone showed lymphopenia. Pathology was remarkable for pulmonary edema in PA/LF treated rat lungs and pulmonary hemorrhage in PA/EF treated rat lungs. These results are consistent with our and others' previous findings that the morbidity and mortality associated with anthrax are not cytokine-mediated but due to a direct effect of the toxins on the cardiovascular system along with toxin-specific alterations in blood counts. PA/LF pathology matches that seen with acute cardiac failure, and PA/EF pathology coincides with direct vascular endothelial injury. These observations provide a rational basis for drug interventions to reduce the effect of these toxins on the heart and blood vessels.

Original languageEnglish (US)
Pages (from-to)467-472
Number of pages6
JournalMicrobial Pathogenesis
Volume44
Issue number6
DOIs
StatePublished - Jun 1 2008

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Keywords

  • Anthrax edema toxin
  • Anthrax lethal toxin
  • Heart failure
  • Vascular injury

ASJC Scopus subject areas

  • Microbiology
  • Infectious Diseases

Cite this

Kuo, S. R., Willingham, M. C., Bour, S. H., Andreas, E. A., Park, S. K., Jackson, C., Duesbery, N. S., Leppla, S. H., Tang, W. J., & Frankel, A. E. (2008). Anthrax toxin-induced shock in rats is associated with pulmonary edema and hemorrhage. Microbial Pathogenesis, 44(6), 467-472. https://doi.org/10.1016/j.micpath.2007.12.001