Related Experiment Video
Updated: Jul 17, 2026
Long Term Chronic Pseudomonas aeruginosa Airway Infection in Mice
Published on: March 17, 2014
Cathepsin-G interferes with clearance of Pseudomonas aeruginosa from mouse lungs
Julia Sedor1, Lisa Hogue, Kathryn Akers
1Mallinkrodt Department of Pediatrics, WA University School of Medicine, St. Louis, MO 63110, USA.
Abstract:
The cystic fibrosis airway is susceptible to Pseudomonas aeruginosa infection, which stimulates an intense inflammatory response leading to airway obstruction and bronchiectasis. Neutrophils migrate into the airway, and once there, release high concentrations of neutral serine proteases during phagocytosis and in death. In particular, neutrophil elastase is central to progression of bronchiectasis by interfering with bacterial clearance and directly perpetuating the inflammatory response in the airway. Using a murine model of endobronchial inflammation, we found that a different neutrophil-derived serine protease, cathepsin G, inhibited the host's ability to clear Pseudomonas from the lung, based on a 1-log reduction in bacteria recovered from cathepsin G-deficient mice. Higher antibody concentrations were found in respiratory epithelial lining fluid from mice lacking cathepsin G, but there was no difference in other opsonins, such as surfactant proteins A and D. Chemokine levels measured in the lung correlated with bacterial burden and not the animal's genotype, indicating that airway inflammation was not affected by the presence (or absence) of specific serine proteases. These findings suggest that cathepsin G interferes with airway defenses, showing that proteases other than neutrophil elastase have roles in the pathogenesis of suppurative airway diseases.
Insights
Cathepsin G, a neutrophil protease, impairs the lung
Area of Science:
- Pulmonary immunology
- Microbial pathogenesis
Background:
- Cystic fibrosis airways are prone to Pseudomonas aeruginosa infection, causing inflammation and airway obstruction.
- Neutrophils release serine proteases, like neutrophil elastase, which contribute to bronchiectasis progression.
- The role of other neutrophil proteases in airway disease is less understood.
Purpose of the Study:
- To investigate the role of cathepsin G, a neutrophil-derived serine protease, in Pseudomonas aeruginosa infection in a murine model.
- To determine if cathepsin G affects bacterial clearance and host defense mechanisms in the lung.
Main Methods:
- Utilized a murine model of endobronchial inflammation.
- Compared bacterial burden in wild-type and cathepsin G-deficient mice after Pseudomonas aeruginosa challenge.
- Measured antibody and opsonin concentrations in respiratory epithelial lining fluid.
- Assessed chemokine levels in lung tissue.
Main Results:
- Cathepsin G-deficient mice showed improved clearance of Pseudomonas aeruginosa from the lung (1-log reduction).
- Higher antibody concentrations were observed in the respiratory epithelial lining fluid of cathepsin G-deficient mice.
- No significant differences in surfactant proteins A and D or chemokine levels were found between genotypes.
- Airway inflammation did not appear to be affected by the presence or absence of cathepsin G.
Conclusions:
- Cathepsin G inhibits the host's ability to clear Pseudomonas from the lung.
- Antibodies, but not other opsonins or general inflammation, seem to be the mechanism by which cathepsin G affects bacterial clearance.
- These findings highlight a role for cathepsin G, beyond neutrophil elastase, in the pathogenesis of suppurative airway diseases.
