Related Experiment Video
Updated: May 27, 2026
11:20
Alveolar Macrophage Phagocytosis and Bacteria Clearance in Mice
Published on: March 2, 2019
Anthrax edema toxin impairs clearance in mice
Inka Sastalla1, Shixing Tang, Devorah Crown
1Bacterial Toxins and Therapeutics Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Infection and Immunity
|November 23, 2011
Summary
Anthrax edema toxin (ET) increases circulating levels of protective antigen (PA) and other molecules by upregulating cell receptors and affecting clearance mechanisms. This prolonged circulation may enhance anthrax virulence.
Area of Science:
- Toxicology
- Microbiology
- Pharmacology
Background:
- Anthrax edema toxin (ET) comprises protective antigen (PA) and edema factor (EF).
- ET disrupts host cell functions by increasing cyclic AMP.
- The in vivo consequences of ET action require further elucidation.
Purpose of the Study:
- To investigate the impact of enzymatically active EF on PA serum concentrations in vivo.
- To explore the mechanisms behind altered protein and small molecule pharmacokinetics induced by ET.
- To understand the broader effects of ET on host cell functions and fluid homeostasis.
Main Methods:
- Utilized mouse models of anthrax toxemia and infection.
- Measured serum PA concentrations in the presence of active EF.
- Assessed PA receptor (TEM8, CMG2) expression and PA uptake in vitro and in vivo.
- Evaluated the clearance of various proteins and a small molecule (biotin) coinjected with ET.
- Monitored liver and kidney functional markers and aquaporin-2 activity.
Main Results:
- Active EF significantly increased serum PA concentrations in vivo.
- ET enhanced PA binding and uptake via upregulation of TEM8 and CMG2 receptors.
- ET impaired the clearance of multiple proteins (ovalbumin, GFP, EF) and biotin.
- Altered liver and kidney functional markers and activated kidney aquaporin-2 were observed.
- These effects were independent of general fluid loss.
Conclusions:
- ET actively increases circulating PA levels and alters the pharmacokinetics of various molecules.
- Upregulation of PA receptors and impaired clearance contribute to prolonged circulation of ET components and other substances.
- ET's effects on fluid homeostasis and molecule clearance may prolong the circulation of anthrax virulence factors, potentially enhancing infection severity.
